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

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 Updates

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).¹

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.^1,2 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 FGFR2 fusions or rearrangements who have received prior therapy.³ 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.⁴ 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.⁵ 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.⁶

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.⁵ 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.⁷

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.

Key Global Updates

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.⁸ 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).⁹ The median PFS was 6.3 months with ripretinib vs 1.0 month with placebo (HR, 0.15; 95% CI, 0.09-0.25; P < .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, 2026.⁷ Ripretinib is approved in over 40 countries, including the US and those of the European Union.

References

1. 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
2. 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
3. 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
4. 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/
5. 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/
6. 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/
7. 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
8. 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
9. 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. Lancet Oncol. 2020;21(7):923-934. doi:10.1016/S1470-2045(20)30168-6