April’s gastrointestinal (GI) regulatory landscape was characterized by a surge in specialized FDA designations aimed at accelerating the development of precision tools for difficult-to-treat malignancies. Of note, the FDA granted priority review to zanidatamab-hrii (Ziihera)–based regimens for HER2-positive gastroesophageal adenocarcinoma (GEA) and accepted a supplemental biologics license application (sBLA) for zenocutuzumab-zbco (Bizengri) in NRG1 fusion–positive cholangiocarcinoma.1,3
Other key milestones include a first-in-class breakthrough for liquid biopsy in liver cancer and new regulatory support for targeted therapies in pancreatic cancer and hepatocellular carcinoma (HCC). These decisions highlight an ongoing shift toward addressing specific molecular drivers, such as KRAS mutations and hepatitis B virus (HBV)–host genome integration, to overcome historical "blind spots" in the GI oncology space.
Read the roundup below to catch up on the past month’s regulatory developments in gastric cancer, GEA, pancreatic cancer, hepatocellular carcinoma (HCC), and more.
Gastric Cancer
FDA Grants Priority Review to Zanidatamab-Containing Regimens for Frontline HER2+ Gastric Cancer
On April 27, 2026, the FDA accepted and granted priority review to the sBLA for zanidatamab in combination with chemotherapy with or without tislelizumab (Tevimbra) for the frontline treatment of patients with HER2-positive advanced or metastatic gastric, gastroesophageal junction adenocarcinoma, or GEA. The FDA has set a target action date of August 25, 2026, for this application.1
Supporting data from thephase 3 HERIZON-GEA-01 trial (NCT05152147) showed that patients who received the combination of zanidatamab, tislelizumab, and chemotherapy (n = 302) achieved a median progression-free survival (PFS) of 12.4 months (95% CI, 9.8-18.5) vs 8.1 months (95% CI, 7.0-8.9) with standard trastuzumab (Herceptin) plus chemotherapy (HR, 0.63; 95% CI, 0.51-0.78; P < .0001).2 Zanidatamab plus chemotherapy alone (n = 304) also elicited a median PFS of 12.4 months (95% CI, 9.8-14.5; HR, 0.65; 95% CI, 0.52-0.81; P < .0001). The median overall survival (OS) was 26.4 months (95% CI, 21.5-30.3) for the triplet vs 19.2 months (95% CI, 16.8-21.8) with the control regimen (HR, 0.72; 95% CI, 0.57-0.90; P = .0043). The safety profiles of these zanidatamab-based regimens were deemed generally manageable by investigators
Of note, the triplet regimen is the first immuno-oncology combination to show efficacy across both PD-L1–positive and –negative tumors in this clinical setting.1 These findings position zanidatamab-based combinations as potential new first-line standards of care in HCC.
Bile Duct Cancer
FDA Receives sBLA for Zenocutuzumab in NRG1+ Cholangiocarcinoma
On April 15, 2026, an sBLA was submitted to the FDA for zenocutuzumab for the treatment of adult patients with advanced unresectable or metastatic NRG1 fusion–positive cholangiocarcinoma.3 Concurrent with this submission, the National Comprehensive Cancer Network (NCCN) added the agent to its Clinical Practice Guidelines in Oncology for biliary tract cancers as a Category 2A-recommended subsequent-line therapy and Category 2B-recommended frontline treatment for this specific population.4
The submission is based on data from the phase 1/2 eNRGy study (NCT02912949), where the cholangiocarcinoma cohort achieved an overall response rate (ORR) of 36.8% (95% CI, 16.3%-61.6%) and a median duration of response (DOR) of 12.9 months with the agent per blinded independent central review (BICR).3 Zenocutuzumab was generally well tolerated, with no patients discontinuing treatment due to adverse effects.
This decision addresses a significant unmet need for patients with rare NRG1 gene fusions, who typically face limited treatment options and poor clinical outcomes.
GI Regulatory Highlights From April
- The FDA granted priority review to zanidatamab-based regimens and accepted an sBLA for zenocutuzumab, signaling momentum in HER2-positive GEA and NRG1 fusion–positive cholangiocarcinoma, respectively.
- Multiple expedited designations, including breakthrough device status for the CatCHimera liquid biopsy and fast track designation for the pan-KRAS inhibitor BBO-11818, underscore a shift toward biomarker-driven innovation.
- Additional regulatory actions, including orphan drug designation for tovecimig, reflect ongoing efforts to address unmet needs across biliary tract cancers, HCC, and pancreatic cancer.
HCC
FDA Grants Orphan Drug Designation to Tovecimig for HCC
On April 8, 2026, the FDA granted orphan drug designation to tovecimig (CTX-009/ABL001), a bispecific antibody targeting DLL4 and VEGF-A, for the treatment of bile duct cancer.5 The drug is currently being developed by ABL Bio’s global partner, Compass Therapeutics.
This designation is supported by data from the ongoing phase 2/3 COMPANION-002 trial (NCT05506943). Topline findings reported in April 2025 showed that the study met its primary ORR end point with tovecimig plus paclitaxel (n = 111) vs paclitaxel alone (n = 57); ORRs were 17.1% and 5.3%, respectively, translating to a relative improvement of 11.8% (P = .031).6
Additional data shared on April 27, 2026, showed that the agent met a key secondary end point of the trial, with a median PFS by BICR of 4.7 months with tovecimig vs 2.6 months with paclitaxel (HR, 0.44; P < .0001).7 Despite this PFS benefit, the study did not meet its other secondary end point of OS, largely due to a high rate of crossover from the control arm (54%; n = 31/57). No new safety signals were reported.
Tovecimig previously received FDA fast track designation and orphan drug designation for the treatment of patients with metastatic or locally advanced biliary tract cancers.6
First Viral-Integration MRD Liquid Biopsy Granted FDA Breakthrough Device Designation in HCC
On April 21, 2026, TCM Biotech received FDA breakthrough device designation for CatCHimera, a liquid biopsy minimal residual disease (MRD) platform for HCC.8 Unlike traditional assays that rely on somatic mutations, CatCHimera uses HBV-host genome integration junctions as tumor-specific biomarkers for monitoring patients after curative treatment.
The platform’s efficacy is supported by clinical data published in Hepatology, which showed that vh-DNA was detected in 98% of pre-surgical plasma with a mean lead time of 158 days over CT for detecting recurrence. The assay demonstrated a negative predictive value of 92% and a positive predictive value of 71% for post-operative recurrence. When combined with AFP and PIVKA-II, the platform achieved 95.8% sensitivity and 95.5% specificity.
As the first viral integration MRD liquid biopsy platform in HCC, this novel circulating tumor DNA biomarker class could address high recurrence rates in HCC following resection.
Pancreatic Cancer
Pan-KRAS Inhibitor BBO-11818 Receives FDA Fast Track Designation for Pancreatic Cancer
On April 20, 2026, The FDA granted fast track designation to BBO-11818 for the treatment of adult patients with advanced KRAS-mutant pancreatic ductal adenocarcinoma (PDAC). BBO-11818 is a selective, non-covalent pan-KRAS inhibitor designed to target KRAS in both its "ON" and "OFF" states, specifically addressing mutations like KRAS G12D and G12V where targeted options have historically been limited.9
The designation is based on preliminary results from the phase 1 KONQUER-101 trial (NCT06917079) in patients with locally advanced or metastatic KRAS-mutant solid tumors. Data shared in January 2026 showed that the agent produced a partial response in a patient with PDA, with a 56% reduction in tumor size.10 Tumor reductions were also observed at higher dose levels. Moreover, the BBO-11818 monotherapy appeared to be well tolerated, with no dose-limiting toxicities; treatment-related adverse effects were primary GI-related.
This decision is critical because it allows for closer collaboration with the FDA to expedite the review of a therapy for PDAC, one of the most aggressive malignancies with a significant unmet need for targeted treatments.
References
- Jazz Pharmaceuticals announces FDA acceptance and priority review of supplemental biologics license application for Ziihera (zanidatamab-hrii) combinations in first-line HER2+ locally advanced or metastatic GEA. News release. Jazz Pharmaceuticals. April 27, 2026. Accessed May 1, 2026. https://investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-announces-fda-acceptance-and-priority-0
- Elimova E, Rha SY, Shitara K, et al. Zanidatamab + chemotherapy (CT) ± tislelizumab for first-line (1L) HER2-positive (HER2+) locally advanced, unresectable, or metastatic gastroesophageal adenocarcinoma (mGEA): primary analysis from HERIZON-GEA-01. J Clin Oncol. 2026, 44(suppl 4):LBA285. doi:10.1200/JCO.2026.44.2_suppl.LBA285
- Partner Therapeutics announces submission of supplemental biologics license application (sBLA) to FDA for Bizengri (zenocutuzumab-zbco) in NRG1 fusion positive cholangiocarcinoma and inclusion in updated NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). News release. Partner Therapeutics. April 14, 2026. Accessed May 1, 2026. https://www.partnertx.com/partner-therapeutics-announces-submission-of-supplemental-biologics-license-application-sbla-to-fda-for-bizengri-zenocutuzumab-zbco-in-nrg1-fusion-positive-cholangiocarcinoma-and-inclusion-i/
- NCCN. Clinical Practice Guidelines in Oncology. Biliary tract cancers, version 1.2026. March 10, 2026. Accessed May 1, 2026. https://www.nccn.org/professionals/physician_gls/pdf/btc.pdf
- ABL Bio's US partner wins FDA's orphan drug designation for bile duct cancer drug Tovecimig. News Release. Korea Biomed. April 8, 2026. Accessed May 1, 2026. https://www.koreabiomed.com/news/articleView.html?idxno=31224
- Tovecimig demonstrates statistically significant benefit in COMPANION-002 randomized phase 2/3 study in patients with biliary tract cancer. News Release. Compass Therapeutics. April 27, 2026. Accessed May 1, 2026. https://investors.compasstherapeutics.com/news-releases/news-release-details/tovecimig-demonstrates-statistically-significant-benefit
- Tovecimig (CTX-009) meets primary endpoint in the ongoing randomized phase 2/3 study in patients with biliary tract cancer. News release. Compass Therapeutics. April 1, 2025. Accessed May 1, 2026. https://investors.compasstherapeutics.com/news-releases/news-release-details/tovecimig-ctx-009-meets-primary-endpoint-ongoing-randomized
- FDA breakthrough for first viral-integration MRD liquid biopsy in HCC—new ctDNA biomarker class. News Release. PR Newswire. April 21, 2026. Accessed May 1, 2026. https://www.prnewswire.com/news-releases/fda-breakthrough-for-first-viral-integration-mrd-liquid-biopsy-in-hcc--new-ctdna-biomarker-class-302748497.html
- BBOT granted U.S. FDA fast track designation for BBO-11818 for the treatment of adult patients with advanced KRAS-mutant pancreatic ductal adenocarcinoma. News Release. BBOT. April 20, 2026. Accessed May 1, 2026. https://investors.bbotx.com/news-releases/news-release-details/bbot-granted-us-fda-fast-track-designation-bbo-11818-treatment
- BBOT announces new clinical data advancing its portfolio of three innovative and differentiated RAS and PI3Kα pipeline programs. News Release. BBOT. January 7, 2026. Accessed April 21, 2026. https://investors.bbotx.com/news-releases/news-release-details/bbot-announces-new-clinical-data-advancing-its-portfolio-three
