The FDA has accepted and granted priority review to a new drug application (NDA) seeking the approval of lirafugratinib (RLY-4008) as a second-line treatment option for patients with pretreated cholangiocarcinoma (CCA) harboring

The regulatory agency has assigned a Prescription Drug User Fee Act target action date of September 27, 2026.

The NDA submission was supported by findings from the phase 1/2 ReFocus trial (NCT04526106).

 Among evaluable patients in the pivotal cohort, patients with FGFR inhibitor–naive CCA who had previously received chemotherapy (n = 114) achieved an objective response rate (ORR) of 46.5% (95% CI, 37.1%-56.1%) with lirafugratinib per independent review committee (IRC) assessment. Best overall response rates included a complete response rate of 2.6%, a partial response rate of 43.9%, and a stable disease rate of 50.0%.

 Moreover, the disease control rate (DCR) was 96.5% (95% CI, 91.3%-99.0%), with a median duration of response (DOR) of 11.8 months (95% CI, 7.5-13.0). The median progression-free survival (PFS) and overall survival (OS) were 11.3 months (95% CI, 9.2-14.8) and 22.8 months (95% CI, 18.1-27.2), respectively. Of note, these data were shared during the 

“Lirafugratinib has established a compelling clinical profile that differentiates it from existing treatment options,” Dong-Gun Kim, chief executive officer of Elevar Therapeutics, stated in a news release.

 “We are very pleased with the FDA’s priority review designation and focused on advancing the review process efficiently to bring this therapy to patients as quickly as possible.”

Data from an efficacy analysis of the pivotal cohort in ReFocus were shared at the 2026 Gastrointestinal Cancers Symposium; this cohort comprised patients who were FGFR inhibitor–naive but had previously received chemotherapy.

Lirafugratinib achieved an IRC-assessed ORR of 46.5% (95% CI, 37.1%-56.1%), a DCR of 96.5% (95% CI, 91.3%-99.0%), and a median DOR of 11.8 months (95% CI, 7.5-13.0).

The safety profile of lirafugratinib was consistent with those commonly associated with on-target FGFR2 inhibition; the most common grade 3 or higher treatment-related AEs were nail toxicities, palmar-plantar erythrodysesthesia, and stomatitis.

What was the design of the ReFocus trial?

The ReFocus study is an open-label, first-in-human trial evaluating the safety and efficacy of lirafugratinib, a potent, selective, oral small molecule inhibitor of FGFR2, in patients with advanced or metastatic solid tumors harboring 

 The trial includes dose-escalation (part 1), dose-expansion (part 2), extension (part 3), and rollover (part 4) components.

Eligible patients across all 4 parts were at least 18 years of age with histologically or cytologically confirmed unresectable or metastatic solid tumors with documented

fusions, mutations, or amplifications, measurable disease per RECIST 1.1 criteria, and an ECOG performance status of 0 or 1.

 Patients were also required to have disease that was refractory to or had not adequately responded to standard therapies, or for which no standard treatment options were available.

In part 1, patients received escalating doses of oral lirafugratinib to establish the recommended phase 2 dose (RP2D). In part 2, patients with CCA were stratified into 4 cohorts based on 

 alteration type and prior exposure to chemotherapy or FGFR inhibitors and were treated with continuous daily lirafugratinib at the RP2D of 70 mg.

The primary end point for the pivotal cohort was confirmed ORR per RECIST 1.1 criteria by IRC.

 Key secondary end points included DOR, DCR, PFS, OS, safety, and quality of life (QOL) as assessed by the EORTC Core QOL questionnaire.

What should be known about lirafugratinib’s safety profile?

Lirafugratinib demonstrated a predictable and manageable safety profile, with adverse effects (AEs) mitigated through dose modifications.

The most common any-grade and grade 3 or higher treatment-related AEs (TRAEs) in the ReFocus pivotal safety population (n = 116) were nail toxicities (87.9%; 12.1%), palmar-plantar erythrodysesthesia (81.9%; 32.8%), stomatitis (78.4%; 12.1%), and retinal pigment epithelial detachment (37.1%; 1.7%).

 TRAEs leading to dose reduction, dose interruption, and treatment discontinuation were reported in 75.9%, 82.8%, and 4.3% of these patients, respectively.

Elevar Therapeutics announces FDA acceptance for review of new drug application for lirafugratinib as second-line cholangiocarcinoma treatment. News Release. Elevar. March 30, 2026. Accessed March 30, 2026. https://www.globenewswire.com/news-release/2026/03/30/3264531/0/en/Elevar-Therapeutics-Announces-FDA-Acceptance-for-Review-of-New-Drug-Application-for-Lirafugratinib-as-Second-line-Cholangiocarcinoma-Treatment.html

Hollebecque A, Borad MJ, Lu P, et al. Efficacy and safety of lirafugratinib in FGFRi-naive cholangiocarcinoma (CCA) patients harboring FGFR2 fusions/rearrangements (FGFR2 f/r). 

. 2026;44(suppl 2):476. doi:10.1200/JCO.2026.44.2_suppl.476

REFOCUS: a first-in-human study of highly selective FGFR2 inhibitor, RLY-4008, in patients with ICC and other advanced solid tumors ClinicalTrials.gov. Updated February 27, 2026. Accessed March 30, 2026. https://clinicaltrials.gov/study/NCT04526106

An NDA for lirafugratinib in pretreated, FGFR2-altered cholangiocarcinoma was accepted for FDA review and assigned a PDUFA date of September 27, 2026.

FDA Grants Priority Review to Lirafugratinib for FGFR2+ Pretreated Cholangiocarcinoma

©Image by Ashling Wahner & MJH Life Sciences Using AI

Many people with lung cancer can be treated with a highly precise, high dose of radiation given in just one session — without compromising the effectiveness of the treatment. That’s the striking conclusion of 

, of Roswell Park Comprehensive Cancer Center that has the potential to change the treatment recommendations for many patients with a common form of lung cancer.

The new treatment strategy, outlined in a new publication in the International Journal of Radiation Oncology, Biology, Physics, could offer multiple benefits for many patients who cannot undergo lung cancer surgery — fewer side effects from radiation exposure, less disruption to their lives and, possibly, lower medical costs.

Lung cancer is the leading cause of cancer death in the United States, and a type known as non-small cell lung cancer (NSCLC) accounts for about 85% of those cases. When patients with early-stage lung cancer cannot undergo surgery because of their age, condition or other reasons, typically they are treated with stereotactic body radiation therapy (SBRT), a form of medical radiation that precisely targets tumors to avoid damaging healthy tissues nearby.

One session instead of three — but just as effective

Looking at how well patients responded to treatment over a six-year period, Dr. Singh and his colleagues from Roswell Park, the Cleveland Clinic’s Taussig Center and the State University of New York Upstate Medical Center in Syracuse show that reducing both the radiation dose and the number of treatment sessions results in the same long-term results as a higher dose delivered over more treatment sessions. They found that one session at half the usual radiation dose works just as well as three higher‑dose sessions. That means:

No increase in radiation-related side effects

Much less time spent traveling to and from appointments

“Single-fraction stereotactic body radiation therapy to peripheral lung tumors is cheaper, more convenient and just as effective,” says Dr. Singh.

The clinical trial followed 98 patients with early-stage NSCLC whose tumors were located in the outer parts of the lung and who were not able to undergo surgery. Participants were randomly assigned to one of two approaches:

3 fraction SBRT: 60 gray (Gy, or units) of radiation, delivered over three sessions

One Fraction SBRT: 30 Gy delivered in one session

Patients were monitored regularly for up to five years. The research team found no meaningful differences between the two groups in survival, cancer recurrence or side effects.

“This is an easy way to lower costs and increase convenience for patients without compromising on cancer control,” says Dr. Singh. “This approach may be even more important to those patients who must travel large distances to receive radiation.”

6-year Roswell Park study shows shorter, lower-dose approach works just as well as longer course of treatment



Lung Cancer Patients Can Safely Receive Half the Usual Radiation Dose — in Just One Treatment

The FDA has approved denosumab-adet (Ponlimsi) as a biosimilar to denosumab (Prolia) for all indications of the reference product.

The FDA approval of Ponlimsi was backed by a totality of evidence, including analytical and clinical data showing similar efficacy, safety, and immunogenicity profiles of the biosimilar compared with reference denosumab. Ponlimsi is approved for all indications of the reference product, including the treatment of postmenopausal women with osteoporosis at high risk for fracture, to increase bone mass in men with osteoporosis at high risk for fracture, the management of glucocorticoid-induced osteoporosis in men and women at high risk for fracture, to increase bone mass in men at high risk for fracture who are receiving androgen deprivation therapy for the management of nonmetastatic prostate cancer, and to increase bone mass in women at high risk for fracture who are receiving adjuvant aromatase inhibitor therapy for the management of breast cancer.

“Our biosimilars R&D engine continues to demonstrate its depth and maturity. By combining deep internal expertise with strategic partnerships, we’re building a highly competitive portfolio,” Steffen Nock, PhD, head of biosimilars R&D and chief science officer at Teva, stated in a news release. “With a strong early-stage pipeline and a suite of advancing programs, we see significant potential to address patient needs and fuel Teva’s long-term growth.”

The FDA has approved Ponlimsi as a biosimilar to denosumab for all indications of the reference product.

The FDA approval of Ponlimsi was based on a totality of evidence, including analytical and clinical data demonstrating similar efficacy, safety, and immunogenicity profile as denosumab.

In November 2025, the European Commission granted marketing authorization to Ponlimsi following a positive opinion from the Committee for Medicinal Products for Human Use.

What is the regulatory history of Ponlimsi?

In November 2025, the European Commission granted marketing authorization to Ponlimsi following a positive opinion from the Committee for Medicinal Products for Human Use earlier in 2025.

 The regulatory decision indicated the biosimilar for the management of osteoporosis in postmenopausal women and men who are at increased risk of fractures, the treatment of bone loss associated with hormone ablation in men with prostate cancer who are at increased risk of fractures, and the treatment of bone loss in adult patients receiving long-term treatment with systemic glucocorticoids.

Ponlimsi carries a safety warning for severe hypocalcemia in patients with advanced kidney disease.

 Patients with advanced chronic kidney disease (defined by an eGFR < 30 mL/min/1.73 m

), including dialysis-dependent patients, have a greater risk of severe hypocalcemia following denosumab product administration. Moreover, the presence of chronic kidney disease-mineral bone disorder significantly increases the risk of hypocalcemia in these patients. Prior to beginning treatment with Ponlimsi, patients with advanced chronic kidney disease should be evaluated for the presence of chronic kidney disease-mineral bone disorder; patients in this group who receive Ponlimsi should be supervised with a health care provide with expertise in the diagnosis and management of chronic kidney disease-mineral bone disorder.

Ponlimsi is contraindicated in patients with hypocalcemia, pregnant women, and patients with hypersensitivity to denosumab products. The biosimilar also carries warnings and precautions for mineral metabolism changes, concomitant use of drug products with same active ingredient, osteonecrosis of the jaw, atypical subtrochanteric and diaphyseal femoral fractures, multiple vertebral fractures following discontinuation of treatment, serious infections, dermatologic adverse reactions, musculoskeletal pain, suppression of bone turnover, and hypercalcemia in pediatric patients with osteogenesis imperfecta.

“The FDA approval of Ponlimsi is a significant milestone that showcases our robust clinical, analytical, operational and regulatory expertise,” Yolanda Tibbe, global head of biosimilars at Teva, added in the news release. “To receive US FDA approval of Ponlimsi…truly underscores the strength of our expanding global biosimilar portfolio and reaffirms our commitment to expand treatment options for patients.”

Teva gains biosimilar momentum with U.S. FDA approval of Ponlimsi (denosumab-adet) and dual filing acceptance for biosimilar candidate to Xolair (omalizumab). News release. Teva. March 30, 2026. Accessed March 30, 2026. https://ir.tevapharm.com/news-and-events/press-releases/press-release-details/2026/Teva-Gains-Biosimilar-Momentum-with-U-S--FDA-Approval-of-PONLIMSI-denosumab-adet-and-Dual-Filing-Acceptance-for-Biosimilar-Candidate-to-Xolair-omalizumab/default.aspx

Teva receives European Commission approvals for Ponlimsi (denosumab) biosimilar to Prolia and Degevma (denosumab) biosimilar to Xgeva. News release. Teva. November 25, 2025. Accessed March 30, 2026. https://www.tevausa.com/news-and-media/press-releases/teva-receives-european-commission-approvals-for-ponlimsi-denosumab-biosimilar-to-prolia-and-degevma-/

The biosimilar Ponlimsi is approved for all reference denosumab indications, and applications for an omalizumab biosimilar candidate have been accepted.

Denosumab-Adet Gains FDA Approval for All Indications of Denosumab

TKIs have proliferated within the chronic myeloid leukemia (CML) treatment paradigm, with second- and third-generation agents, in addition to alternative formulations, presenting patients with CML with more diverse options, according to Michael J. Mauro, MD.

Mauro specifically highlighted the FDA approval of the generic, small molecule formulation of dasatinib (Phyrago) for patients with CML and acute lymphoblastic leukemia, which is the only approved formulation of the TKI that can be administered concomitantly with proton pump inhibitors (PPIs) and H

 receptor antagonists intended to help patients manage acid reflux.

“We’ve grown accustomed to counseling patients that they need to follow a certain schedule if they have to take a drug twice a day on an empty stomach to eliminate or minimize the effect of acid blockade, for example,” Mauro said. “With [this newly approved dasatinib] formulation, we can now introduce them in the beginning [of treatment].”

, Mauro also dived into the phase 3 ASC4FIRST trial (NCT04971226), which evaluated asciminib (Scemblix) for the treatment of CML.

 He also touched on the roles other TKIs, such as ponatinib (Iclusig), bosutinib (Bosulif), imatinib (Gleevec), and nilotinib (Tasigna), play in CML management, and detailed ongoing research aiming to refine TKI use for this patient population.

Mauro is an attending physician at Memorial Sloan Kettering Cancer Center in New York, New York.

How do you make decisions between the currently approved TKIs for the treatment of CML?

Managing a patient with CML, at present in 2026, is what we call it a spoil of riches. We have a number of different choices, and a lot depends on where [patients are] at in the course of [their disease]. The most important decision is: how do we choose a frontline therapy, where have actually have multiple approved options?

We have some compelling data from a recent study, the ASC4FIRST trial, which looked at asciminib vs imatinib or other second-generation TKIs, [and asciminib superiority] was the case. In a well-designed trial, we saw that asciminib offered a lower adverse effect [AE] profile and superior response, which puts it at the top of our list.

 There are questions that people have regarding long-term safety [of asciminib in CML], which should be resolved by looking at long-term data from the phase 1 study [NCT02081378], where we have more than 10 years [of follow-up].

Of course, we also have other [TKIs available in CML] that are viable. We have our second-generation TKI dasatinib, which is the best option based on risk/reward, flexibility, and [the fact that] it's a TKI that can be started at lower doses. Lower doses can be easily adapted if a patient has tolerability issues or if they have a preference.

Other second-generation TKIs are also good in the frontline and offer advantages, but they also [feature] different AEs. We want to steer away from serious and morbid AEs like cardiovascular [AEs]. Imatinib, which was our original TKI, has the longest safety [follow-up, in addition to being] available as a generic. [Imatinib] offers good efficacy and predictable safety.

Frontline therapy is complicated—probably the most complicated [for TKI selection in CML]. [After considering each available TKI,] we look at response, comorbidities, and mutations. [The role of mutations is] becoming a bit more of a prominent story with more use of asciminib, where we have a more selective resistance profile. We don't see more resistance [to asciminib], but we do see a more selective and perhaps a more TKI mutation–dominant resistance signature. [There is also a] question about secondary mutations in the myeloid genome spectrum outside [

] that may be relevant to choosing a TKI and how a patient is responding.

The patient has to be part of this [treatment] discussion because this is a long journey. It's like running a marathon, [thus] fully assessing the patient's comorbidities, particularly their cardiovascular status, seeing where they're at in their disease course, [and having a] full discussion and communication during treatment [is necessary] because intolerance is an equal challenge to clinical response and clinical benefit. Making careful decisions and striking that balance [between efficacy and safety] is probably the most important thing to remember when approaching TKI selection in CML.

What improvements have you seen with later-generation TKIs in CML?

The story of TKI development with CML unfolded with the first principle about developing a small molecule inhibitor against BCR-ABL1. Imatinib was the canonical prototype molecule [for TKIs in CML], which turned out to be safe, highly effective, and revolutionary. [Imatinib is] what we call an active site inhibitor, [which] binds the ATP binding pocket.

[Following imatinib], we developed second-generation ATP competitive inhibitors, which were dasatinib, nilotinib, and bosutinib. [The second-generation agents] have different properties with regard to the way they bind the BCR-ABL1 kinase domain. They also have different AEs, which is where the risk:benefit analysis comes into play.

Imatinib has a predictable AE profile, where musculoskeletal symptoms, gastrointestinal [GI] AEs, and fluid retention [are] challenges to consistent use and the patient quality of life, rather than significant or morbid AEs. As we got into the second- and third-generation inhibitors, we started to see questions about morbid AEs, such as vascular AEs, including vascular occlusion, and pleural and pericardial complications. With bosutinib, we saw more intense versions of the AEs seen with imatinib, such as more intense GI toxicities and liver enzyme elevation.

We then developed the third-generation TKIs, and ponatinib tried to solve the question: what do we [to combat] selective resistance with the presence of a 

 T315I mutation? T315I mutations make binding of the ATP pocket complicated. [However], via a different molecular structure and binding at the active site, ponatinib was able to overcome this mutation and not have any mutations for which resistance would be expected. [Ponatinib] offered a tremendous advantage for patients with highly resistant or heavily pretreated disease.

[Ponatinib,] of course, was studied all the way into the frontline, but unfortunately, the AE profile for the drug carried forward into earlier lines of therapy, [prompting us] to halt those trials. [Thus,] we still relegate ponatinib to later-line therapy when most [other] drugs have already been used, where it serves patients well but has the highest risk of cardiovascular and vascular occlusive AEs.

Asciminib is in its own class. It specifically targets the myristoyl pocket, [which] is another region in the BCR-ABL1 kinase domain that is targetable and was known from the beginning to be a way to essentially inactivate BCR-ABL1. By correcting a defect called the myristoyl pocket, which occurs with 

 fusion, [asciminib] essentially puts the kinase into an inactive state, generating programmed cell death.

Eventually, oral, safe, small molecules were developed. The biggest challenge moving forward now is going to be: how do we use [these TKIs] together? How do we choose [between all TKIs]? There are also other drugs in development, including novel allosteric inhibitors. For a while, we have seen the search for a better active site inhibitor, and there's some good candidates that are far along in clinical development.

What are the clinical implications of the generic, small-molecule FDA approval of dasatinib that allows for concomitant use of PPIs?

In addition to the continued development of specific and alternative approaches to BCR-ABL1 inhibition, we've seen a nice addition with multiple alternative formulations of available drugs. We've seen approval of alternative forms of nilotinib, which are able to be taken without food exclusion. Importantly, we have a [newly approved] formulation of dasatinib, with several others in development [The generic, small molecule approval of dasatinib now allows patients to have concomitant therapy to block stomach acid and correct for stomach pH through histamine blockade or more commonly PPI.

[These formulations] allow for a patient to overcome barriers. It can often be a challenge to getting full adherence, absorption, and effect from their TKI. [Full absorption and adherence to TKIs] can be unknowingly or knowingly undermined by concomitant medications, dosing difficulties, and requirements such as fasting.

[There is also] an oral liquid formulation of imatinib, which could be a very significant advance for pediatric patients or older patients who might have issues with the mechanics of oral medications. [Ultimately, there] will be more to come, and this is an important space to develop—not just to develop better and more potent TKIs, but rather to optimize the drugs and compounds that are already available.

How do different formulations of agents affect how you approach TKI selection in CML?

If a patient needs a drug for their CML and there's an alternative formulation, at present, with multiple iterations available, a discussion is always important. We’ve grown accustomed to counseling patients that they need to follow a certain schedule if they have to take a drug twice a day on an empty stomach to eliminate or minimize the effect of acid blockade, for example. With [the newly approved dasatinib] formulation, we can now introduce [PPIs] in the beginning [of treatment]. We have our standard formulations, which have certain requirements, and if that isn't feasible, one can quickly pivot to alternate formulations.

Newly FDA approved generic, small molecule formulation of dasatinib enables patients who require concomitant medications to fully absorb dasatinib.

Patient factors and AE profiles help drive TKI selection and sequencing in CML.

Allosteric inhibitors and other novel TKIs have shown promise in early phase studies, as researchers aim to continue refining TKIs in this space.

What is most important is looking at the bulk of patients who remain on treatment who may have questions about their ability to easily and effectively take their drug, [in addition to] raising awareness. There may not be as much awareness of these novel agents, which are in the mix with generic forms of dasatinib and may not be as well understood. There is different dosing, for example, for one of the alternative formulations of nilotinib, and there's different dosing for certain forms that may be developed regarding dasatinib. We don't want confusion about the dose; we want to make it clear that we have multiple options and want to prescribe the right drug for the right patient and circumstance.

We now have a new class of therapy with allosteric inhibitors, which we've seen better efficacy and safety [early in development]. The holy grail for CML is: can we increase the cure fraction if we're able to increase the number of patients who are eligible for what's called a treatment-free remission? [Treatment-free remissions are] when patients have had sufficient length of treatment and deep remission that meets defined requirements, who then elect to be closely monitored off therapy.

There's some speculation that asciminib, for example, may increase the success of treatment-free remission for patients with the same remission they might have achieved with one of our earlier-generation TKIs. This remains to be proven, but it is exciting to think about.

Despite better and safer drugs, we still have patients with resistance and intolerance. [Thus,] continued development of alternate active site inhibitors [is important]. I'm excited about a drug [ELVN-001] from a company called Enliven Therapeutics, which is an ATP competitive agent and is moving through trials nicely, proving to be safe and highly effective in challenging cases.

We have drugs that are in similar spaces, that have been approved outside the US, such as olverembatinib, which has been studied primarily in Asia but requires further scrutiny and may have some unique features regarding its dosing and AEs. Alternative allosteric inhibitors are the [fastest-growing] area of development. We have a nice dossier from a company called Terns Pharmaceuticals with a drug TERN-701, which may offer advantages over asciminib. With data in patients who had previous asciminib and ponatinib exposure, the patients seem to be doing quite well comparatively with earlier data. We may have a second version of allosteric inhibitors that could offer advantages over asciminib. There are other allosteric inhibitors in development, as well.

We’re not done. We have still unmet needs, particularly in the fact that the more options we have for our patients, the better this spoiler riches will be for our patients, [so we can] offer them as many options as we can. CML should be a highly treatable and functionally curable disease, and the more options we have, the better.

Treatment for CML is like a marathon. You have to be prepared, knowledgeable, thoughtful, and patient. You have to check in along the way because [CML seems] like it may be easy to treat, but we get lost sometimes when we're not paying attention to AEs or response trajectories. We want we want to stay on course, stay in the game, engage in dialogue, and follow-up [with patients to ensure] tremendous success.

Phyrago. Prescribing information. Updated August 2025. Accessed March 27, 2026. https://phyrago.com/wp-content/uploads/2025/10/FPI-0041-Phyrago-Pediatric-inclusive-PI-final.pdf

Hughes T, Hochhaus A, Takahashi N et al. ASC4FIRST, a pivotal phase 3 study of asciminib (ASC) vs investigator-selected tyrosine kinase inhibitors (IS TKIs) in newly diagnosed patients (pts) with chronic myeloid leukemia (CML): Primary results. 

. 2024;42(17). doi:10.1200/JCO.2024.42.17_suppl.LBA6500

Michael J. Mauro, MD, discusses the variety of TKIs available for chronic myeloid leukemia management and how to navigate new formulations.

New TKI Formulations Engender New Horizons for CML Treatment Possibilities

©Image by Ashling Wahner & MJH Life Sciences

March’s top regulatory updates in gastrointestinal (GI) malignancies were primarily pipeline related, with endorsement of a pivotal phase 3 trial design for an oncolytic virus in pancreatic cancer and a potential accelerated approval pathway for a novel Claudin 18.2–directed therapy in gastric cancer. Additional regulatory milestones were reached in the US and abroad, with the FDA approval of a companion diagnostic for esophageal and gastroesophageal junction (GEJ) carcinomas, FDA orphan drug designation for RCT1213 in hepatocellular carcinoma (HCC), and submission of a marketing application for ripretinib in Japan for gastrointestinal stromal tumors (GISTs).

Read the roundup below to catch up on the past month’s regulatory developments in gastric cancer, pancreatic cancer, hepatocellular carcinoma (HCC), and GIST.

FDA Approves PD-L1 IHC 22C3 pharmDx for Esophageal or GEJ Carcinoma

On March 26, 2026, the FDA approved Agilent Technologies Inc’s PD-L1 IHC 22C3 pharmDx (SK006) as a companion diagnostic to identify patients with esophageal or GEJ carcinoma who may be eligible for treatment with pembrolizumab (Keytruda).

With this decision, PD-L1 IHC 22C3 pharmDx now has 8 indications across 7 tumor types and is the only FDA-approved companion diagnostic in gastric or GEJ adenocarcinoma that can identify potential candidates for the agent whose tumors express PD-L1. 

Of note, pembrolizumab in combination with fluoropyrimidine- and platinum-containing chemotherapy is indicated for the treatment of patients with metastatic or locally advanced esophageal or GEJ (tumors with epicenter 1-5 cm above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation, and whose tumors express PD-L1 with a combined positive score of at least 1.

 Data from the phase 3 KEYNOTE-590 trial (NCT03189719) supported the FDA’s decision to grant traditional approval to the combination in March 2021.

FDA Grants Priority Review to Lirafugratinib in Second-Line Cholangiocarcinoma 

On March 30, 2026, the FDA accepted and granted priority review to the new drug application seeking the approval of lirafugratinib (RLY-4008) for the treatment of patients with cholangiocarcinoma harboring 

 fusions or rearrangements who have received prior therapy.

 Lirafugratinib is a potent, selective, oral small molecule inhibitor of FGFR2. 

The submission was supported by data from the phase 1/2 ReFocus trial (NCT04526106), which demonstrated a confirmed overall response rate of 46.5% with lirafugratinib in the indicated patient population. A Prescription Drug User Fee Act target action date of September 27, 2026, has been assigned.

FDA Aligns on Accelerated Approval Pathway for Givastomig in First-Line Gastric Cancer

On March 16, 2026, the FDA confirmed the potential eligibility of givastomig (TJ033721/ABL111) for an accelerated approval pathway in first-line HER2-negative, Claudin (CLDN) 18.2–positive, PD-L1-positive gastroesophageal cancer (GEC) in alignment with the drug’s developer, NovaBridge Biosciences.

 The decision follows a productive Type B meeting and is supported by data from a phase 1b trial (NCT04900818) evaluating givastomig in combination with nivolumab (Opdivo) and modified FOLFOX6 (oxaliplatin, fluorouracil, and leucovorin calcium [(folinic acid]).

In the phase 1b expansion study, the combination demonstrated an overall response rate (ORR) of 75% among evaluable patients (n = 52). Patients who received givastomig at the 8 mg/kg dose (n = 26) achieved an ORR of 77%, a median progression-free survival (PFS) of 16.9 months (95% CI, 6.8-not applicable [NA]), and a 6-month PFS rate of 73% (95% CI, 51.7%-86.2%). In the 12-mg/kg cohort (n = 26), these respective values were 73% (7.7 months; 95% CI, 6.9-NA) and 91% (95% CI, 69.0%-97.7%).

Givastomig is a bispecific antibody that conditionally activates T cells via the 4-1BB pathway only in the presence of tumors expressing CLDN 18.2. NovaBridge intends to initiate a registrational phase 3 combination trial as early as the fourth quarter of 2026, using ORR as the primary end point for accelerated approval. If approved, givastomig could serve as a first-in-class and best-in-class CLDN 18.2–targeted therapy for the above patient population.

FDA Endorses Phase 3 Trial Design for Oncolytic Adenovirus in Metastatic PDAC

On March 23, 2026, the FDA gave general agreement on the design of a pivotal phase 3 clinical trial for zabilugene almadenorepvec (VCN-01) in combination with gemcitabine and nab-paclitaxel (Abraxane) for the first-line treatment of metastatic pancreatic ductal adenocarcinoma (PDAC) following a Type B End-of-Phase 2 meeting.

 Zabilugene almadenorepvec is a systemically administered oncolytic adenovirus designed to replicate in tumor cells and degrade the tumor stroma.

The proposed phase 3 trial will build on the phase 2b VIRAGE study (NCT05673811), which met its primary end point of improved overall survival (OS) and safety with zabilugene almadenorepvec plus gemcitabine/nab-paclitaxel in 96 patients with newly diagnosed metastatic PDAC.

The proposed phase 3 study is planned as a randomized, double-blind trial comparing zabilugene almadenorepvec plus gemcitabine/nab-paclitaxel with gemcitabine/nab-paclitaxel plus placebo.

 The FDA agreed on proposed dosing, a primary end point of OS, key secondary end points including progression-free survival, and the use of an adaptive design featuring repeated “macrocycles” of zabilugene almadenorepvec. In accordance with prior guidance from the European Medicines Agency’s Committee for Medicinal Products for Human Use, the FDA indicated that a successful study could support a biologics licensing application for the agent in metastatic PDAC.

RCT1213 Receives FDA Orphan Drug Designation for HCC

On March 24, 2026, the FDA granted orphan drug designation to RCT1213 for the treatment of patients with HCC. RCT1213 is a first-in-class antibody targeting TM4SF5, designed to modulate the tumor microenvironment through a mechanism distinct from existing checkpoint inhibitors.

The designation is supported by data from preclinical and early studies showing activity in models resistant to current checkpoint inhibitors. ReCerise Therapeutics, the drug’s developer, is currently advancing global clinical development through a partnership with the National Cancer Centre Singapore.

Manufacturing and Marketing Approval for Ripretinib in GIST Under Consideration in Japan

On March 26, 2026, Ono Pharmaceutical submitted an application for the manufacturing and marketing approval of ripretinib (DCC-2618) in Japan for patients with GISTs that have progressed following chemotherapy.

 The application is based on results from the global phase 3 INVICTUS study (NCT03353753), which evaluated ripretinib at 150 mg daily against placebo in patients previously treated with 3 or more tyrosine kinase inhibitors, including imatinib (Gleevec).

In the INVICTUS study, ripretinib significantly prolonged the primary end point of progression-free survival (PFS) compared with placebo and produced a clinically meaningful improvement in overall survival (OS).

 The median PFS was 6.3 months with ripretinib vs 1.0 month with placebo (HR, 0.15; 95% CI, 0.09-0.25; 

 < .0001). The median OS was 15.1 months vs 6.6 months, respectively (HR, 0.36; 95% CI, 0.21-0.62). The regimen also had an acceptable safety profile, and the most common treatment-related treatment-emergent adverse effect was alopecia (49%).

Notably, ripretinib received orphan drug status for the above indication in Japan on March 19, 2026.

 Ripretinib is approved in over 40 countries, including the US and those of the European Union.

Agilent receives FDA approval for PD-L1 IHC 22C3 pharmDx in gastric or gastroesophageal junction (GEJ) adenocarcinoma. News release. Agilent Technologies Inc. March 26, 2026. Accessed March 26, 2026. https://www.agilent.com/about/newsroom/presrel/2026/26mar-ca26009.html?srsltid=AfmBOorTEeeQIM1KxWodPxgt0nP7Jos5lQCo3WmBwlOZEWkBXd8ek_rd

FDA approves pembrolizumab for esophageal or GEJ carcinoma. FDA. March 22, 2021. Accessed March 26, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-esophageal-or-gej-carcinoma

Elevar Therapeutics announces FDA acceptance for review of new drug application for lirafugratinib as second-line cholangiocarcinoma treatment. News release. Elevar Therapeutics, Inc. March 30, 2026. Accessed March 30, 2026. https://www.globenewswire.com/news-release/2026/03/30/3264531/0/en/Elevar-Therapeutics-Announces-FDA-Acceptance-for-Review-of-New-Drug-Application-for-Lirafugratinib-as-Second-line-Cholangiocarcinoma-Treatment.html

NovaBridge announces productive FDA Type B meeting on potential accelerated approval pathway for givastomig in gastric cancer. News release. NovaBridge Biosciences. March 16, 2026. Accessed March 26, 2026. https://www.novabridge.com/news-releases/news-release-details/novabridge-announces-productive-fda-type-b-meeting-potential/

Theriva Biologics announces positive End-of-Phase 2 meeting with US FDA regarding the design of a phase 3 trial of VCN-01 in metastatic pancreatic ductal adenocarcinoma. News release. Theriva Biologics. March 23, 2026. Accessed March 26, 2026. https://therivabio.com/press_releases/theriva-biologics-announces-positive-end-of-phase-2-meeting-with-u-s-fda-regarding-the-design-of-a-phase-3-trial-of-vcn-01-in-metastatic-pancreatic-ductal-adenocarcinoma/

Theriva Biologics announces primary end points for efficacy and safety achieved in VIRAGE phase 2b clinical trial of VCN-01 with gemcitabine/nab-paclitaxel in newly diagnosed metastatic pancreatic cancer patients (NCT05673811). Theriva Biologics. News release. May 7, 2025. Accessed March 26, 2026. https://therivabio.com/press_releases/theriva-biologics-announces-primary-endpoints-for-efficacy-and-safety-achieved-in-virage-phase-2b-clinical-trial-of-vcn-01-with-gemcitabine-nab-paclitaxel-in-newly-diagnosed-metastatic-pancre/

Kim JH. ReCerise Therapeutics’ RCT1213 wins FDA orphan drug designation for liver cancer. Korea Biomedical Review. ReCerise Therapeutics. March 24, 2026. Accessed March 26, 2026. https://www.koreabiomed.com/news/articleView.html?idxno=31042

Ono Pharma submits an application for approval of ripretinib (DCC-2618) in patients with advanced gastrointestinal stromal tumor in Japan. News release. Ono Pharmaceutical Co, Ltd. March 26, 2026. Accessed March 26, 2026. https://www.ono-pharma.com/en/news/20260326.html

Blay JY, Serrano C, Heinrich MC, et al. Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial. 

. 2020;21(7):923-934. doi:10.1016/S1470-2045(20)30168-6

We recap the top regulatory decisions of March in GI malignancies.

March’s GI Monthly Rewind: Diagnostic Developments and FDA Alignments You Need to Know

The investigational erdafitinib (Balversa) intravesical drug-releasing system (Erda-iDRS; TAR-210) demonstrated preliminary efficacy and tolerability in patients with non–muscle-invasive bladder cancer (NMIBC) harboring select 

 alterations, according to findings from a phase 1 study (NCT05316155) presented during the 

Erda-iDRS, an investigational erdafitinib intravesical drug-releasing system, demonstrated preliminary efficacy and tolerability in patients with 

Patients with high-risk disease experienced a median RFS of 20 months (95% CI, 15-30). Those with intermediate-risk disease achieved a median CR duration of 18 months (95% CI, 14-25).

In the overall population, TRAEs leading to treatment discontinuation and interruption occurred at respective rates of 9.1% and 4.5%, and there were no TRAEs that led to death.

At a median follow-up of 24 months (range, 15-30), findings from the final analysis of the first-in-human study revealed that patients who were treated with Erda-iDRS in cohort 1 (n = 26) experienced a median recurrence-free survival (RFS) of 20 months (95% CI, 15-30). The 12-month RFS rate in cohort 1 was 83% (95% CI, 62%-93%).

 In cohort 3 (n = 55), the 6-month complete response (CR) rate was 89% (95% CI, 78%-95%). The median follow-up duration in responders was 18 months (range, 15-21) and the median CR duration was also 18 months (95% CI, 14-25).

“Erda-iDRS achieved proof-of-concept for sustained local delivery of erdafitinib and demonstrated preliminary clinical activity in patients with 

-altered NMIBC,” Antoni Vilaseca, MD, PhD, MSc, an adjunct physician of the Urology Service at Hospital Clínic de Barcelona in Spain, said during the presentation. 

The open-label, multicenter study enrolled patients with 

-altered intermediate- and high-risk NMIBC.

 Cohort 1 enrolled patients with high-risk, recurrent, high-grade Ta/T1 papillary-only disease with no carcinoma in situ; patients in this cohort were also required to have received BCG, not undergone radical cystectomy, and undergo transurethral resection of bladder tumor prior to treatment with Erda-iDRS. Cohort 3 enrolled patients with intermediate-risk, recurrent disease with a history of low-grade only Ta/T1 disease and visible target lesions prior to treatment.

During the dose-escalation portion of the study (part 1), patients received Erda-iDRS at an approximate dose of 2 mg per day up to 4 mg per day; Erda-iDRS placement occurred every 3 months. In the dose-expansion portion (parts 2 and 3), patients received Erda-iDRS at an approximate dose of 2, 3, or 4 mg per day.

The primary end point was safety. Secondary end points included RFS in cohort 1, CR rate and duration in cohort 3, and pharmacokinetic measures.

At baseline, the median ages in cohorts 1 and 3 were 72.5 years (range, 37.0-90.0) and 68.5 years (range, 41.0-89.0), respectively. Most patients in both cohorts were male (73.1% vs 77.4%), White (80.8% vs 61.3%), had stage Ta disease (80.8% vs 96.8%), and had an ECOG performance status of 0 (65.4% vs 83.9%). Every patient in both cohorts underwent surgery or another procedure prior to enrollment. Other prior anticancer therapies included intravesical BCG (100% vs 22.6%), intravesical chemotherapy (23.1% vs 53.2%), and systemic therapy (3.8% vs 0%).

What were the safety data that were shared during the EAU Congress?

In terms of safety, patients in the overall population (n = 88) experienced any-grade treatment-related adverse effects (TRAEs) at a rate of 67.0%. The most common any-grade TRAEs that were reported in at least 10% of patients consisted of hematuria (31.8%), dysuria (21.6%), pollakiuria (14.8%), micturition urgency (14.8%), urinary tract infection (13.6%), and bladder spasm (10.2%). TRAEs leading to treatment discontinuation (9.1%) and interruption (4.5%) were reported, and there were no TRAEs that led to death.

Grade 3 or higher TRAEs occurred at a rate of 4.5%. Serious TRAEs consisted of pyelonephritis (n = 1), sepsis (n = 1), and hematuria (n = 1). No hyperphosphatemia or retinal toxicities were observed.

“[Erdafitinib] was tolerable, with mostly grade 1 or 2 lower urinary tract symptoms,” Vilaseca said. “Phase 2 and 3 trials of Erda-iDRS are ongoing in patients with 

-altered NMIBC in the MoonRISe program.”

Vilaseca received honoraria from Astellas Pharma, Johnson & Johnson/Janssen, Recordati, and Bayer; consulting/advisory fees from Johnson & Johnson/Janssen, Astellas Pharma, Recordati, and Accord Healthcare; and travel expenses from Ipsen and Recordati.

Vilaseca A, Li R, Meeks J, et al. Final analysis of the phase 1 first-in-human study of erda-iDRS, an erdafitinib intravesical drug-releasing system, in patients with non–muscle-invasive bladder cancer harboring select FGFR alterations. Presented at: 

 EAU Congress; March 13-16, 2026; London, United Kingdom. Abstract LB008.

Johnson & Johnson highlights promising first-in-human erda-iDRS (formerly TAR-210) results in intermediate‑risk non–muscle-invasive bladder cancer. News release. Johnson & Johnson. March 13, 2026. Accessed March 27, 2026. https://www.jnj.com/media-center/press-releases/johnson-johnson-highlights-promising-first-in-human-erda-idrs-formerly-tar-210-results-in-intermediate-risk-non-muscle-invasive-bladder-cancer

Study of erdafitinib intravesical delivery system for localized bladder cancer. ClinicalTrials.gov. Updated March 13, 2026. Accessed March 27, 2026. https://clinicaltrials.gov/study/NCT05316155?term=NCT05316155&viewType=Card&rank=1

Erda-iDRS was safe and produced early efficacy signals in FGFR-altered NMIBC.

Erda-iDRS Is Safe and Active in FGFR-Altered NMIBC

Welcome to The Five Under 5, your go-to roundup of the top 5 videos of the week.

These short videos are designed for busy oncologists to view on the go, and feature expert insights on breaking news, regulatory updates, practice-changing data shared at medical meetings, and other key topics in the realm of oncology.

Examining the ENVISION Trial in NMIBC: Sandip M. Prasad, MD

, of Atlantic Health, discusses previous findings from the phase 3 ENVISION trial (NCT05243550) that evaluated complete response (CR) rates and duration of response (DOR) by EORTC recurrence score subgroups in patients with recurrent low-grade intermediate-risk non–muscle-invasive bladder cancer. The single-arm, open-label study examined mitomycin (UGN-102), a novel non-surgical chemoablative gel therapy that can be administered outpatient without discontinuing blood thinners, in 240 patients with the primary end point of 3-month CR rate. In those who received all 6 planned doses, the 3-month CR rate was 80% (95% CI, 73.9%-84.5%), with a response probability of 82% (95% CI, 75.9%-87.1%) at 1 year, a median DOR that was not estimable at a median follow-up of 13.9 months, and a favorable toxicity profile with 57% of patients experiencing a treatment-emergent adverse effect. Prasad concluded that these data provide powerful evidence supporting the efficacy of chemoablative therapy, with subsequent post hoc analyses presented at the 

Potential Role of the Microbiome in Early-Onset CRC: John L. Marshall, MD

, of the Otto J. Ruesch Center for the Cure of Gastrointestinal Cancers and Georgetown Lombardi Comprehensive Cancer Center, discusses the rising incidence of early-onset colorectal cancer (CRC) and its defining clinical characteristics in recognition of CRC Awareness Month. Unlike traditional CRC, where roughly 40% of tumors arise on the right side and 60% on the left, early onset CRC is characterized by an overwhelming predominance of left-sided distal tumors, frequently at the rectosigmoid junction, suggesting it is a biologically distinct disease entity. Marshall noted that microbiome alterations potentially driven by dietary or environmental factors concentrated in the distal colon could serve as a primary oncogenic catalyst, comparing the current state of research to Darwin's observation of natural selection before the mechanisms were fully understood. He noted that although similar rising cancer trends are observed in breast and other gastrointestinal malignancies among young adults, the phenomenon is most pronounced in CRC, and solving the microbiome's role could have broad downstream implications for treating other young-adult cancers.

Value of the Breast Cancer Index for Assessing Disease Recurrence Risk: Sami Diab, MD

, of the Center for Cancer and Blood Research of Pagosa Springs Medical Center, highlights the clinical utility and prognostic significance of the Breast Cancer Index (BCI) in patients with breast cancer receiving adjuvant endocrine therapy. Although BCI is most commonly linked with decision making for extended adjuvant therapy in the 5-to-10-year post-diagnosis window, Diab clarified that the assay is also validated as a prognostic tool for early recurrence in the 0-to-5-year interval, providing comprehensive risk insight across a full 10-year trajectory. During the early treatment phase, oncologists must choose among options like aromatase inhibitors or tamoxifen, and for premenopausal patients, the decision of whether to incorporate ovarian suppression presents a particular clinical challenge where more data are still needed. By leveraging BCI's dual prognostic capabilities spanning both early and late recurrence windows, Diab concluded that endocrine therapy strategies can more effectively be tailored to each patient's individual risk profile.

Understanding How Patient Goals Drive TKI Selection in CML: Jorge Cortes, MD

, of the Georgia Cancer Center of Augusta University, explains how prioritizing individual patient goals is the most important factor when selecting an initial TKI for the treatment of patients with chronic myeloid leukemia. Although disease risk classifications and other clinical factors also inform treatment decisions, Cortes underscored that common patient priorities like finishing therapy quickly, minimizing adverse effects (AEs), maximizing quality of life, or managing cost often narrow the available TKI options to a manageable set. Practical considerations like dosing schedule and food requirements must also be weighed with patient goals. He added that comorbidities are particularly important as they can predispose patients to AEs linked with specific TKIs. After initial therapy, Cortes noted that treatment responses, reported AEs, and mutation profiles all play a key role in guiding subsequent TKI selections, a process he described as ultimately more complex than the initial decision.

Evolving AI Risk-Stratification Methods in Multiple Myeloma: C. Ola Landgren, MD, PhD

, of the Sylvester Myeloma Institute and the University of Miami Miller School of Medicine, unpacks evolving risk-stratification strategies in multiple myeloma management and the development of the CORAL AI tool in honor of Multiple Myeloma Awareness Month. Researchers at the University of Miami built individualized prediction models trained on large datasets integrating disease biology, clinical characteristics, and treatment data to better estimate patient outcomes and guide dynamic clinical decision making. CORAL is a histomorphologic deep learning platform designed to extract meaningful biological insights directly from routine bone marrow biopsy images, inferring underlying molecular characteristics and genomic abnormalities typically obtained through advanced sequencing addressing the common real-world limitations of comprehensive genomic profiling. By integrating histopathology image analysis with clinical and treatment variables, CORAL enables real-time, individualized risk assessment and treatment guidance even where detailed molecular data are unavailable.

The top 5 OncLive TV videos of the week cover insights in bladder cancer, colorectal cancer, breast cancer, chronic myeloid leukemia, and multiple myeloma.

Five Under 5: Top Oncology Videos for the Week of 3/22

Talazoparib plus enzalutamide significantly improved rPFS versus enzalutamide alone in HRR-mutated mCSPC in phase 3 TALAPRO-3, surpassing the prespecified hazard ratio target and showing consistent benefit across BRCA and non-BRCA alterations. An interim analysis also showed a favorable OS trend. Key secondary endpoints, including ORR, DOR, and time to PSA progression, favored the combination. Safety aligned with known profiles without new signals. Findings may support regulatory discussions and earlier-line precision use.

Enolen was safe and feasible for the treatment of patients with early-stage prostate cancer.

Latest News

Latest News

FDA Grants Priority Review to Lirafugratinib for FGFR2+ Pretreated Cholangiocarcinoma

Lung Cancer Patients Can Safely Receive Half the Usual Radiation Dose — in Just One Treatment

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New TKI Formulations Engender New Horizons for CML Treatment Possibilities

March’s GI Monthly Rewind: Diagnostic Developments and FDA Alignments You Need to Know

Erda-iDRS Is Safe and Active in FGFR-Altered NMIBC

Five Under 5: Top Oncology Videos for the Week of 3/22

Novel Enzalutamide Delivery Implant Is Safe and Active in Early-Stage Prostate Cancer

The OncFive: Top Oncology Articles for the Week of 3/22

Gotistobart Shows Potential as Chemo-Free Option for Treatment-Resistant Squamous NSCLC

CHMP Recommends Tarlatamab for Relapsed ES-SCLC

OncLive Weekly News Quiz (3/27/2026): Test Your Knowledge on Ovarian, Lung Cancer Updates and More

Sac-TMT Extends OS in Pretreated EGFR-Mutated NSCLC

China Approves Neoadjuvant T-DXd Followed by THP for HER2+ Breast Cancer

CHMP Recommends SC Isatuximab Via On-Body Injector for Multiple Myeloma