May’s GI Monthly Rewind: A Landmark Approval in CCA, Expanded Access for Daraxonrasib, and More Key Pipeline Updates

The global gastrointestinal regulatory landscape doesn't slow down, and May was no exception. The month's headline was the FDA's landmark approval of zenocutuzumab-zbco (Bizengri) for NRG1 fusion–positive cholangiocarcinoma, the first targeted therapy cleared for this rare biliary malignancy.¹ In pancreatic ductal adenocarcinoma (PDAC), May also brought a pivotal moment for the pan-RAS inhibitor daraxonrasib (RMC-6236), with the FDA issuing a “safe to proceed” letter for an expanded access protocol—enabling patients outside clinical trials to access what many are calling the most impactful drug in pancreatic cancer in more than a decade.²

Significant global updates include a positive opinion for encorafenib (Braftovi) plus cetuximab (Erbitux) and FOLFOX (fluorouracil, leucovorin, and oxaliplatin) in first-line, BRAF V600E–mutant metastatic colorectal cancer (mCRC) in the European Union, and a third breakthrough therapy designation (BTD) for a first-in-class PD-1/IL-2α-bias bispecific fusion protein in mCRC in China.^3,4

Read on for the full month in review.

FDA Updates

FDA Authorizes Expanded Access to Daraxonrasib in Previously Treated Metastatic PDAC

On May 1, 2026, the FDA issued a “safe to proceed” letter to Revolution Medicines, authorizing the initiation of an expanded access treatment protocol (EAP) for daraxonrasib for patients with previously treated metastatic PDAC.² The authorization follows Revolution Medicines’ announcement on April 13, 2026, of its intent to submit a new drug application (NDA) for daraxonrasib under the FDA’s Commissioner’s National Priority Voucher pilot program. Notably, the FDA received the expanded access request on April 28 and signed it within 2 days—a turnaround that FDA Commissioner Marty Makary, MD, MPH, stated “reflects the FDA’s strong commitment to facilitate early access to therapies for serious and life-threatening conditions, including pancreatic cancer.”

The expanded access authorization is underpinned by data from the pivotal phase 3 RASolute 302 trial (NCT06625320), in which daraxonrasib met all primary and secondary efficacy end points and nearly doubled median overall survival (OS).⁵ In the dual primary analysis population of patients with RAS G12 mutations, daraxonrasib (n = 228) reduced the risk of death by 60% vs chemotherapy (n = 231; HR, 0.40; 95% CI, 0.30-0.54; P = 5.9 × 10⁻¹⁰). At a median follow-up of 8.5 months (range, 3.2-15.9), the median OS was 13.2 months (95% CI, 10.0-not estimable [NE]) compared with 6.6 months (95% CI, 5.4-8.2), respectively. The median PFS was 7.3 months (95% CI, 6.3-8.1) with daraxonrasib (n = 228) vs 3.5 months (95% CI, 2.9-3.8) with chemotherapy (HR, 0.45; 95% CI, 0.34-0.59; P = 3.2 × 10⁻⁹).

Prior FDA designations for daraxonrasib include BTD (June 2025), orphan drug designation, and a Commissioner’s National Priority Voucher (October 2025).²

FDA Approves Zenocutuzumab for NRG1 Fusion–Positive Advanced Cholangiocarcinoma

On May 8, 2026, the FDA approved zenocutuzumab-zbco (Bizengri) for the treatment of adults with advanced, unresectable, or metastatic cholangiocarcinoma harboring a NRG1 fusion with disease progression on or after prior systemic therapy.¹ This decision marks the first targeted therapy approved specifically for NRG1 fusion–positive cholangiocarcinoma.

The approval is supported by efficacy and safety data from the cholangiocarcinoma cohort of the phase 2 eNRGy trial (NCT02912949), an open-label, registrational, multicenter basket study evaluating zenocutuzumab across multiple solid tumor types harboring NRG1 gene fusions. In the cholangiocarcinoma cohort, zenocutuzumab demonstrated an overall response rate (ORR) of 36.8% (95% CI, 16.3%-61.6%) per blinded independent central review and a median duration of response (DOR) of 12.9 months. Notably, no patients discontinued treatment due to adverse effects (AEs). The safety profile of zenocutuzumab in the eNRGy trial was characterized by predominantly grade 1/2 AEs. Infusion-related reactions (IRRs) occurred in 13% of patients, of which 91% occurred during the first infusion; these were all grade 1 or 2.

This approval, combined with prior NCCN guideline inclusion as a Category 2A-recommended subsequent-line therapy and Category 2B-recommended frontline treatment for NRG1 fusion–positive cholangiocarcinoma, provides the first approved targeted option for this patient population.

FDA Grants FTD to Suplexa in MSI-H CRC

On May 13, 2026, the FDA granted fast track designation to the non-engineered autologous cellular immunotherapy suplexa for the treatment of patients with microsatellite instability–high (MSI-H) colorectal cancer (CRC).⁶

This regulatory decision was supported by results from the phase 1, first-in-human SUPLEXA-101 study (NCT05237206). Final efficacy and safety data from the study showed signals of antitumor activity with suplexa across patients with solid tumors (n = 35), most notably in MSI-H CRC. Regarding safety, no dose-limiting toxicities, treatment-related serious AEs or injection-site reactions were reported in the overall study population; moreover, treatment-emergent AEs were mild and self-limiting.

A phase 2 open-label trial combining suplexa with checkpoint inhibitors is planned. Concurrently with the fast track designation, Alloplex confirmed the submission of its US investigational new drug application package for suplexa in CRC-MSI-H.

FDA Accepts NDA and Grants Priority Review to Bezuclastinib Plus Sunitinib in Imatinib-Pretreated GIST

On May 28, 2026, the FDA accepted and granted a priority reviewt o a new drug application (NDA) seeking the approval of bezuclastinib (CGT0486) in combination with sunitinib (Sutent) for the treatment of patients with gastrointestinal stromal tumors (GISTs) who have received prior treatment with imatinib (Gleevec).⁷

The application is supported by data from the phase 3 PEAK trial (NCT05208047). At the September 30, 2025, data cutoff, the bezuclastinib combination generated a 50% reduction in the risk of disease progression or death vs standard-of-care sunitinib monotherapy (HR, 0.50; 95% CI, 0.39-0.65; P < .0001).⁸ The median progression-free survival (PFS) was 16.5 months with the combination vs 9.2 months with sunitinib monotherapy. The objective response rate (ORR) was 46% vs 26% with these respective regimens (P < .0001).

Bezuclastinib previously received BTD from the FDA for this indication and was also assigned real-time oncology review following the readout of initial data from PEAK in November 2025.⁷ A target action date of November 30, 2026, has been set by the FDA for the application under the Prescription Drug User Fee Act.

Global Updates

NMPA Grants Third BTD to IBI363 for MSS/pMMR Metastatic CRC

On May 10, 2026, China’s National Medical Products Administration (NMPA) Center for Drug Evaluation granted a third BTD to IBI363 in combination with bevacizumab (Avastin), for the treatment of patients with advanced microsatellite stable or proficient mismatch repair (MSS/pMMR) CRC who progressed on at least 2 prior lines of standard therapy.³

At the 2025 ASCO Annual Meeting, phase 1 data from two studies (NCT05460767, NCT06717880) showed that IBI363 plus bevacizumab (n = 73; 91.8% MSS/pMMR) produced a confirmed ORR of 15.1% and a DCR of 61.6%, with a median PFS of 4.7 months at a median follow-up of 9.9 months.¹² Notably, among patients without liver metastases (n = 32), the confirmed ORR rose to 31.3%, the DCR was 81.3%, and the median PFS reached 7.4 months.

A phase 3 trial is planned to initiate in China in the near term, and Innovent is also conducting studies of IBI363 in the United States and Australia.³

CHMP Issues Positive Opinion for Encorafenib Plus Cetuximab and FOLFOX in First-Line BRAF V600E–Mutant Metastatic CRC

On May 25, 2026, the European Medicines Agency’s Committee for Medicinal Products for Human Use issued a positive opinion recommending the approval of encorafenib in combination with cetuximab and FOLFOX for the first-line treatment of adult patients with BRAF V600E–mutant metastatic colorectal cancer (mCRC).⁴

The positive opinion is based on results from the phase 3 BREAKWATER trial (NCT04607421), which demonstrated statistically significant improvements in both dual primary end points of ORR and PFS, as well as an OS benefit, with the combination. The regimen reduced the risk of death by 51% vs chemotherapy with or without bevacizumab. Full PFS and OS data from BREAKWATER cohort 3 were presented at the 2026 ASCO Annual Meeting.¹³

In the United States, the FDA granted full traditional approval to encorafenib plus cetuximab and fluorouracil-based chemotherapy (mFOLFOX6 or FOLFIRI) in first-line BRAF V600E–mutant mCRC in February 2026, converting the regimen’s prior accelerated approval from December 2024. A final marketing authorization decision from the European Commission (EC) is anticipated later in 2026. If approved, the regimen would be the first and only BRAF-directed therapy approved for first-line treatment of BRAF V600E–mutant mCRC in the EU.⁴

References

1. Flaherty C. FDA approves zenocutuzumab for NRG1 fusion+ cholangiocarcinoma. OncLive. May 8, 2026. Accessed June 1, 2026. https://www.onclive.com/view/fda-approves-zenocutuzumab-for-nrg1-fusion-cholangiocarcinoma
2. Flaherty C. FDA green lights expanded access protocol for daraxonrasib in pretreated metastatic PDAC. OncLive. May 1, 2026. Accessed June 1, 2026. https://www.onclive.com/view/fda-green-lights-expanded-access-protocol-for-daraxonrasib-in-pretreated-metastatic-pdac
3. Innovent Biologics announces IBI363 (PD-1/IL-2α-bias bispecific fusion protein) received third NMPA breakthrough therapy designation for MSS/pMMR metastatic colorectal cancer. News release. Innovent Biologics. May 10, 2026. Accessed June 1, 2026. https://www.prnewswire.com/news-releases/innovent-announces-ibi363-pd-1il-2-bias-bispecific-fusion-protein-received-third-nmpa-breakthrough-therapy-designation-for-msspmmr-metastatic-colorectal-cancer-302767628.html
4. Pierre Fabre Laboratories receives CHMP positive opinion for Braftovi (encorafenib) in combination with cetuximab and FOLFOX for the first-line treatment of adult patients with BRAFV600E-mutant metastatic colorectal cancer. News release. Pierre Fabre Laboratories. May 25, 2026. Accessed June 1, 2026. https://www.prnewswire.com/news-releases/pierre-fabre-laboratories-receives-chmp-positive-opinion-for-braftovi-encorafenib-in-combination-with-cetuximab-and-folfox-302781057.html
5. Wolpin BM, Wainberg ZA, Hendifar AE, et al. Daraxonrasib, a RAS(ON) multi-selective inhibitor vs chemotherapy in previously treated metastatic pancreatic adenocarcinoma (mPDAC): primary and final analysis from the phase 3 RASolute 302 study. J Clin Oncol. 2026;44(suppl 17):LBA4005. doi:10.1200/JCO.2026.44.17_suppl.LBA4005
6. Flaherty C. Suplexa therapeutic cells receives FDA fast track designation in MSI-H CRC. OncLive. May 13, 2026. Accessed June 1, 2026. https://www.onclive.com/view/suplexa-therapeutic-cells-receives-fda-fast-track-designation-in-msi-h-crc
7. Flaherty C. FDA grants priority review to bezuclastinib plus sunitinib for previously treated GIST. OncLive. May 28, 2026. Accessed June 1, 2026. https://www.onclive.com/view/fda-grants-priority-review-to-bezuclastinib-plus-sunitinib-for-previously-treated-gist
8. 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
9. Rznomics announces U.S. FDA Regenerative Medicine Advanced Therapy Designation granted to ‘RZ-001’ for hepatocellular carcinoma. News release. Rznomics Inc. May 8, 2026. Accessed June 1, 2026. https://www.prnewswire.com/news-releases/rznomics-announces-us-fda-regenerative-medicine-advanced-therapy-designation-granted-to-rz-001-for-hepatocellular-carcinoma-302766762.html
10. RenovoRx announces FDA orphan drug designation granted: oxaliplatin for the treatment of pancreatic cancer. News release. RenovoRx Inc. May 28, 2026. Accessed June 1, 2026. https://www.globenewswire.com/news-release/2026/05/28/3302835/0/en/renovorx-announces-fda-orphan-drug-designation-granted-oxaliplatin-for-the-treatment-of-pancreatic-cancer.html
11. Tempus AI receives FDA approval for tumor-only xT CDx, enabling migration of its entire DNA solid tumor portfolio. News release. Tempus AI. May 29, 2026. Accessed June 1, 2026. https://www.businesswire.com/news/home/20260529144345/en/Tempus-Receives-FDA-Approval-for-Tumor-Only-xT-CDx-Enabling-Migration-of-its-Entire-DNA-Solid-Tumor-Portfolio
12. Innovent Biologics announces clinical data of IBI363 (first-in-class PD-1/IL-2α-bias bispecific antibody fusion protein) from phase 1 clinical studies in advanced colorectal cancer at the 2025 ASCO Annual Meeting. News release. Innovent Biologics. June 1, 2025. Accessed June 1, 2026. https://www.prnewswire.com/news-releases/2025-asco-oral-presentation-innovent-biologics-announces-updated-date-of-ibi363-first-in-class-pd-1il-2-bias-bispecific-antibody-fusion-protein-from-phase-1-clinical-studies-in-advanced-colorectal-cancer-302470217.html
13. Flaherty C. BREAKWATER cohort 3 data support FOLFIRI as a chemo backbone with encorafenib/cetuximab in BRAF V600E+ mCRC. OncLive. May 31, 2026. Accessed June 1, 2026. https://www.onclive.com/view/breakwater-cohort-3-data-support-folfiri-as-a-chemo-backbone-with-encorafenib-cetuximab-in-braf-v600e-mcrc