GI Monthly Rewind: Key Regulatory Updates You May Have Missed in February

February featured an array of regulatory updates across gastrointestinal (GI) cancers. These included the FDA approval of encorafenib (Braftovi) plus cetuximab (Erbitux) and chemotherapy for BRAF V600E–mutant metastatic colorectal cancer (mCRC), and the approval of a first-of-its-kind noninvasive Tumor Treating Fields (TTFields) device, Optune Pax, for locally advanced pancreatic cancer. Additionally, the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) gave a positive recommendation for perioperative durvalumab (Imfinzi) in gastric and gastroesophageal junction (GEJ) cancers.

Catch up on this month’s 8 pivotal pipeline updates below in gastric cancer, hepatocellular carcinoma (HCC), pancreatic cancer, and more.

CRC

FDA Grants Traditional Approval to Encorafenib Plus Cetuximab/Chemotherapy for BRAF V600E+ mCRC

On February 24, 2026, the FDA granted traditional approval to encorafenib in combination with cetuximab and fluorouracil-based chemotherapy for adult patients with BRAF V600E–mutant mCRC.¹ This decision was supported by results from the phase 3 BREAKWATER trial (NCT04607421). In the phase 3 population, the combination achieved an overall response rate (ORR) per blinded independent central review of 61% (95% CI, 52%-70%) compared with 40% (95% CI, 31%-49%) for patients treated with chemotherapy with or without bevacizumab (Avastin; P = .0008). The regimen also demonstrated a significant progression-free survival (PFS) benefit, with a median PFS of 12.8 months (95% CI, 11.2-15.9) vs 7.1 months (95% CI, 6.8-8.5) in the control arm (HR, 0.53; P < .0001). In cohort 3, which was introduced upon amendment to the trial to limit randomization to arms B and C, patients who received the encorafenib combination achieved an ORR of 64% (95% CI, 53%-74%) vs 39% (95% CI, 29%-51%) with the control regimen (P = .0011).

This full approval replaces the regimen’s prior accelerated approval for the same indication announced in December 2024 and requires the use of an FDA-approved companion diagnostic to detect the BRAF V600E mutation.

FDA Accepts NDA for Zanzalintinib Plus Atezolizumab in Pretreated mCRC

On February 2, 2026, the FDA accepted a new drug application (NDA) for zanzalintinib (XL092) in combination with atezolizumab (Tecentriq) for the treatment of adult patients with mCRC who have been previously treated with standard chemotherapy and, if they have RAS wild-type disease, anti-EGFR therapy.² The application is backed by data from the phase 3 STELLAR-303 trial (NCT05425940), which met its primary end point with a median overall survival (OS) of 10.9 months for the combination vs 9.4 months with regorafenib (Stivarga; HR, 0.80; 95% CI, 0.69-0.93; P = .0045) in the intention-to-treat population. The most common adverse effects (AEs) observed with the combination were diarrhea (50%), hypertension (34%), and fatigue (33%).

Notably, the FDA has assigned a Prescription Drug User Fee Act target action date of December 3, 2026.

Fast Track Designation Granted to Pelareorep Combination in KRAS-Mutant mCRC

On February 4, 2026, the FDA granted fast track designation to the oncolytic virus immunotherapy pelareorep (Reolysin) in combination with bevacizumab and FOLFIRI (leucovorin calcium [folinic acid], fluorouracil, and irinotecan hydrochloride) for the second-line treatment of patients with KRAS-mutant, microsatellite-stable mCRC.³ This regulatory milestone was informed by data from the phase 1 REO 022 trial (NCT01274624), which reported an ORR of 33%, a median PFS of 16.6 months, and a median OS of 27.0 months—outcomes that compare favorably with historical standards for bevacizumab plus chemotherapy. Translational findings from the trial also indicated that pelareorep increases KRAS mutation–specific T-cell populations, providing a biological rationale for its use as a precision immunotherapy. A randomized phase 2 study is planned to further evaluate this combination.

Pancreatic Cancer

FDA Approves Optune Pax for Locally Advanced Pancreatic Cancer

On February 12, 2026, the FDA approved Optune Pax, a portable, noninvasive device that delivers TTFields, for use with gemcitabine and nab-paclitaxel (Abraxane) in adults with locally advanced pancreatic cancer.⁴ Data from the phase 3 PANOVA-3 study (NCT03377491) showed a statistically significant 2-month improvement in median OS (16.2 months vs 14.2 months; HR, 0.82; P = .039) with the regimen compared with chemotherapy alone. The device also significantly extended the median time to pain progression to 15.2 months, compared with 9.1 months in the control arm. Although the device was well tolerated without increasing systemic toxicity, device-related skin AEs occurred in 76.3% of patients, most of which were grade 1 or 2.

HCC

FDA Grants Fast Track Designation to Irpagratinib in FGF19-Overexpressing HCC

On February 10, 2026, the FDA granted a fast track designation to irpagratinib (ABSK-011), a selective FGFR4 inhibitor, for the treatment of patients with HCC overexpressing FGF19 who progressed on prior immune checkpoint inhibitors and tyrosine kinase inhibitors.⁵ Data from a phase 1 trial (NCT04906434) presented at the 2024 European Society for Medical Oncology Congress showed that irpagratinib monotherapy achieved an ORR of 46.7% and a median PFS of 5.5 months. Approximately 30% of patients with HCC exhibit FGF19 overexpression, a subgroup with a typically poor prognosis.

The designation is expected to accelerate the global development of this precision therapy, which is also being explored in combination with atezolizumab. Of note, this agent also received a breakthrough therapy designation from the Center for Drug Evaluation of China’s National Medical Products Administration in May 2025.

Gastric and GEJ Cancers

CHMP Recommends Perioperative Durvalumab Regimen for Early-Stage Gastric and GEJ Cancers

On February 2, 2026, the EMA’s CHMP recommended the approval of durvalumab in combination with perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy for adult patients with resectable, early-stage, and locally advanced gastric and GEJ cancers.⁶ The recommendation is based on findings from the phase 3 MATTERHORN trial (NCT04592913), which demonstrated a 29% reduction in the risk of disease progression, recurrence, or death (HR, 0.71; 95% CI, 0.58-0.86; P < .001) and a 22% reduction in the risk of death with the regimen compared with chemotherapy alone. A survival benefit was observed regardless of PD-L1 status, and an estimated 69% of patients in the durvalumab arm were alive at 3 years. If approved by the European Commission, this would become the first immunotherapy-based perioperative therapy in this setting in the EU.

Orphan Drug Designation Granted to HCB101 for Gastric Cancer

On February 13, 2026, the FDA granted an orphan drug designation to HCB101, a next-generation CD47–SIRPα pathway inhibitor, for the treatment of gastric cancer, including HER2-positive and HER2-negative subtypes.⁷ HCB101 is an affinity-optimized SIRPα-IgG4 Fc fusion protein designed to restore macrophage-mediated phagocytosis while minimizing the hematologic toxicities often associated with CD47-targeting therapies. The molecule is currently being evaluated in the ongoing phase 1b/2a HCB101-201 trial (NCT06771622) in combination with standard ramucirumab (Cyramza) and paclitaxel for second-line advanced gastric cancer. In this trial, efficacy-evaluable patients with advanced gastric adenocarcinoma who had progressed after first-line therapy (n = 13) achieved an ORR of 0% at the 2.56-mg/kg dose level and 100% at the 5.12- mg/kg and 8-mg/kg dose levels. Across all doses, the disease control rate was 100%.⁸

Cholangiocarcinoma

Zenocutuzumab Receives Orphan Drug Designation for Cholangiocarcinoma

The FDA granted orphan drug designation to zenocutuzumab-zbco (Bizengri) for the treatment of adults with advanced unresectable or metastatic cholangiocarcinoma harboring an NRG1 gene fusion on February 5, 2026.⁹ Zenocutuzumab is a bispecific antibody that blocks HER2/HER3 dimerization and NRG1 fusion interactions with HER3, suppressing oncogenic signaling pathways.

This designation follows the drug’s prior FDA breakthrough therapy designation for the same patient population in October 2025, which was supported by data from the phase 2 eNRGy trial (NCT02912949). Previously reported efficacy results from the cholangiocarcinoma cohort of the eNRGy trial showed an investigator-assessed ORR of 37% among evaluable patients with advanced NRG1-positive disease (n = 19), alongside a clinical benefit rate of 58%.¹⁰ Of note, the agent has also received FDA accelerated approval for NRG1 fusion–positive non–small cell lung cancer and pancreatic adenocarcinoma.⁹

References

1. Flaherty C. FDA grants full approval to encorafenib plus cetuximab/chemotherapy for BRAF V600E+ mCRC. OncLive.com. February 24, 2026. Accessed February 26, 2026. https://www.onclive.com/view/fda-grants-full-approval-to-encorafenib-plus-cetuximab-chemotherapy-for-braf-v600e-mcrc
2. Flaherty C. FDA accepts NDA for zanzalintinib plus atezolizumab in pretreated mCRC. OncLive.com. February 2, 2026. Accessed February 26, 2026. https://www.onclive.com/view/fda-accepts-nda-for-zanzalintinib-plus-atezolizumab-in-pretreated-mcrc
3. Flaherty C. FDA grants fast track designation to pelareorep plus bevacizumab/FOLFIRI in second-line KRAS-mutant mCRC. OncLive.com. February 4, 2026. Accessed February 26, 2026. https://www.onclive.com/view/fda-grants-fast-track-designation-to-pelareorep-plus-bevacizumab-folfiri-in-second-line-kras-mutant-mcrc
4. Flaherty C. FDA approves Optune Pax for locally advanced pancreatic cancer. OncLive.com. February 12, 2026. Accessed February 26, 2026. https://www.onclive.com/view/fda-approves-optune-pax-for-locally-advanced-pancreatic-cancer
5. Abbisko Therapeutics’ FGFR4 inhibitor irpagratinib granted FDA fast track designation for advanced HCC patients with FGF19 overexpression previously treated with ICIs and mTKIs therapies. News release. Abbisko Therapeutics Co, Ltd. February 10, 2026. Accessed February 26, 2026. https://www.abbisko.com/newsDetail/236.html
6. Imfinzi perioperative regimen recommended for approval in the EU by CHMP for patients with early gastric and gastroesophageal cancers. News release. AstraZeneca. February 2, 2026. Accessed February 26, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/imfinzi-recommended-in-eu-for-early-gastric-cancer.html
7. HanchorBio receives FDA orphan drug designation for HCB101 in gastric cancer. News release. HanchorBio, Inc. February 13, 2026. Accessed February 26, 2026. https://www.hanchorbio.com/en/news/hanchorbio-receives-fda-orphan-drug-designation-for-hcb101-in-gastric-cancer/
8. Yu LA, Ning F, Zhou Z, et al. Dose-dependent antitumor activity of HCB101 plus ramucirumab and paclitaxel in previously treated gastric cancer. J Clin Oncol. 2026;44(suppl 2):372. doi:10.1200/JCO.2026.44.2_suppl.372
9. Zenocutuzumab‑zbco receives FDA orphan drug designation for treatment of cholangiocarcinoma. News release. Partner Therapeutics, Inc. February 5, 2026. Accessed February 26, 2026. https://www.partnertx.com/zenocutuzumab%e2%80%91zbco-receives-fda-orphan-drug-designation-for-treatment-of-cholangiocarcinoma/
10. Schram AM, Cleary JM, Arnold D, et al. Zenocutuzumab efficacy and safety in advanced NRG1+ cholangiocarcinoma: analysis from the phase 2 eNRGy trial. Mol Cancer Ther. 2025;24(suppl 10):A102. doi:10.1158/1535-7163.TARG-25-A102