FDA Flashback: GI Cancer Decisions and News From August 2026

Catch a glimpse of the gastrointestinal cancer–related FDA decisions and announcements from August 2026. These include the approval of an oral RAS(ON) multiselective inhibitor in pretreated metastatic pancreatic cancer and the approval of 2 zanidatamab-based regimens in first-line HER2-positive gastroesophageal adenocarcinoma. The month also brought a complete response letter (CRL) for a radiotherapeutic agent in gastroenteropancreatic neuroendocrine tumors (GEP-NETs), a priority review for a PD-1 inhibitor in mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) locally advanced rectal cancer, a breakthrough therapy designation for a KRAS G12C inhibitor in pancreatic cancer, and 4 fast track designations.

What is the significance of the FDA approval of daraxonrasib in metastatic pancreatic cancer?

On August 26, 2026, the FDA approved daraxonrasib (Rasonque), an oral RAS(ON) multiselective inhibitor, for adult patients with metastatic pancreatic adenocarcinoma who have received at least 1 prior systemic therapy or who are not candidates for multiagent systemic therapy.¹

The approval was based on the global, randomized phase 3 RASolute 302 trial (NCT06625320), in which patients with metastatic pancreatic ductal adenocarcinoma (PDAC) who had received 1 prior fluoropyrimidine- or gemcitabine-based regimen in the metastatic setting were randomly assigned 1:1 to daraxonrasib (n = 248) or investigator’s choice of chemotherapy (n = 252).² Data presented at the 2026 ASCO Annual Meeting showed a median overall survival (OS) in the overall population of 13.2 months (95% CI, 10.0-not estimable) with daraxonrasib vs 6.7 months (95% CI, 5.8-8.0) with chemotherapy (HR, 0.40; 95% CI, 0.30-0.53; P = 4.6×10⁻¹¹). The median progression-free survival (PFS) by blinded independent central review (BICR) was 7.2 months (95% CI, 5.7-7.5) vs 3.6 months (95% CI, 2.9-4.2), respectively (HR, 0.49; 95% CI, 0.38-0.64; P = 5.2×10⁻⁸).

What is the significance of the FDA approval of zanidatamab-based regimens in first-line HER2-positive gastroesophageal adenocarcinoma?

On August 25, 2026, the FDA approved 2 zanidatamab-hrii (Ziihera)–based regimens for the first-line treatment of adults with HER2-positive, unresectable locally advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma, as detected by an FDA-approved test.³ Zanidatamab is approved with fluoropyrimidine- and platinum-containing chemotherapy plus tislelizumab-jsgr (Tevimbra) for immunohistochemistry (IHC) 3+ or IHC 2+/in situ hybridization–positive disease, and with chemotherapy alone for IHC 3+ disease.

The approvals were supported by the phase 3 HERIZON-GEA-01 trial (NCT05152147), which randomly assigned 914 previously untreated patients 1:1:1 to trastuzumab (Herceptin) plus chemotherapy, zanidatamab plus chemotherapy, or zanidatamab plus tislelizumab and chemotherapy.³,⁴ The triplet (n = 302) produced a median PFS by BICR of 12.4 months (95% CI, 9.8-18.5) vs 8.1 months (95% CI, 7.0-8.9) with trastuzumab plus chemotherapy (n = 308; HR, 0.63; 95% CI, 0.51-0.78; P < .0001), as well as a median OS of 26.4 months (95% CI, 21.5-30.3) vs 19.2 months (95% CI, 16.8-21.8), respectively (HR, 0.72; 95% CI, 0.57-0.90; P = .0043).⁴

What is the regulatory status of 177Lu-edotreotide in GEP-NETs?

On August 10, 2026, the FDA issued a CRL to the new drug application (NDA) for the investigational radiotherapeutic agent 177Lu-edotreotide (ITM-11) in patients with GEP-NETs.⁵ The letter cited Chemistry, Manufacturing and Controls items, as well as issues at third-party commercial facilities. The agency did not raise any clinical safety or efficacy concerns and did not request additional clinical or nonclinical data. The developer, ITM, is evaluating next steps, including a future resubmission.

The NDA was supported by the phase 3 COMPETE trial (NCT03049189). The trial randomly assigned patients with unresectable, progressive, grade 1 or 2, somatostatin receptor–positive GEP-NETs 2:1 to 177Lu-edotreotide or everolimus (Afinitor).⁵,⁶ The median PFS per BICR was 23.9 months (95% CI, 18.7-30.0) with 177Lu-edotreotide (n = 207) vs 14.1 months (95% CI, 9.2-20.9) with everolimus (n = 102; HR, 0.67; 95% CI, 0.48-0.95; P = .022).

What is the regulatory status of dostarlimab in dMMR/MSI-H locally advanced rectal cancer?

On August 24, 2026, the FDA granted priority review to a supplemental biologics license application for dostarlimab-gxly (Jemperli). The application covers patients with previously untreated stage II or III dMMR or MSI-H locally advanced rectal cancer.⁷ The FDA assigned a target action date of February 2027 under the Prescription Drug User Fee Act, and the application is also eligible for expedited review through the National Priority Voucher program. Dostarlimab previously received fast track and breakthrough therapy designations in this setting.

The application is supported by data from the phase 2 AZUR-1 trial (NCT05723562). In that trial, patients (n = 154) received dostarlimab monotherapy at 500 mg intravenously every 3 weeks for 9 cycles over 6 months.⁷,⁸ The trial met its primary end point of sustained clinical complete response at 12 months, and full efficacy data are expected to be presented later in 2026.⁷

What is the regulatory status of olomorasib in pretreated KRAS G12C–mutant pancreatic cancer?

On August 3, 2026, the FDA granted breakthrough therapy designation to olomorasib, a next-generation KRAS G12C inhibitor. The designation covers olomorasib monotherapy for patients with advanced pancreatic cancer harboring a KRAS G12C mutation, as determined by an FDA-approved test, who have received at least 1 prior systemic therapy.⁹ No currently approved therapies specifically target KRAS G12C mutations in pancreatic cancer. This is the second breakthrough therapy designation for olomorasib; the first, granted in September 2025, covered the agent plus pembrolizumab (Keytruda) in first-line KRAS G12C–mutant non–small cell lung cancer (NSCLC).

The designation was based on preliminary findings from the phase 1/2 LOXO-RAS-20001 trial (NCT04956640). The trial is evaluating olomorasib alone and in combination regimens in patients with KRAS G12C–mutant advanced solid tumors, including pancreatic cancer.⁹,¹⁰ Primary end points include determination of the recommended phase 2 dose of olomorasib monotherapy, safety, and antitumor activity.¹⁰

What is the regulatory status of ERAS-0015 in metastatic pancreatic adenocarcinoma?

On August 24, 2026, the FDA granted fast track designation to ERAS-0015, an oral pan-RAS molecular glue, for patients with metastatic pancreatic adenocarcinoma.¹¹ In updated preliminary data from the phase 1/1b AURORAS-1 trial (NCT06983743), ERAS-0015 monotherapy at the recommended dose for expansion of 32 mg once daily produced an unconfirmed objective response rate (ORR) at 8 weeks of 57% in patients with second-line or later KRAS G12–mutant PDAC.¹¹ Erasca, the developer, is working with the FDA to plan a phase 3 trial in pancreatic cancer.

What is the regulatory status of SYS6090 in pretreated MSS/pMMR metastatic colorectal cancer?

On August 26, 2026, the FDA granted fast track designation to SYS6090 (JMT108), a PD-1/IL-15 bispecific fusion protein, for patients with microsatellite-stable or mismatch repair–proficient metastatic colorectal cancer (mCRC) that has progressed on standard systemic therapies.¹² CSPC Pharmaceutical Group did not report efficacy data in support of the designation. A phase 1b/2 trial (NCT07750041) is designed to evaluate SYS6090 plus bevacizumab (Avastin), with or without chemotherapy, in advanced colorectal cancer, including a randomized cohort with regorafenib (Stivarga) as the control.¹²,¹³

What is the regulatory status of varsetatug masetecan in relapsed/refractory metastatic colorectal cancer?

On August 27, 2026, the FDA granted fast track designation to varsetatug masetecan (Varseta-M; CX-2051), a masked, conditionally activated, EpCAM-directed antibody-drug conjugate, for patients with relapsed/refractory mCRC.¹⁴ In phase 1 dose-expansion data from the CTMX-2051-101 trial (NCT06265688), the agent produced a confirmed ORR of 32% (n = 6/19) and a median PFS of 7.1 months (95% CI, 3.9-not evaluable) at the 10-mg/kg dose in patients with late-line mCRC.¹⁵ CytomX Therapeutics plans to initiate a potential registrational monotherapy study in the first half of 2027.¹⁴

What is the regulatory status of PLN-101095 plus pembrolizumab in ICI-refractory solid tumors?

On August 18, 2026, the FDA granted fast track designation to PLN-101095, an oral, small molecule, dual-selective inhibitor of integrins αvβ8 and αvβ1, in combination with pembrolizumab for solid tumors resistant to immune checkpoint inhibitors.¹⁶ In previously reported data from the phase 1a/1b FORTIFY trial (NCT06270706), 3 of 6 patients treated with PLN-101095 at 1000 mg twice daily achieved clinical responses; across dose levels, responses were observed in cholangiocarcinoma, head and neck squamous cell carcinoma, melanoma, and NSCLC.¹⁷ Additional FORTIFY data are expected in 2027.¹⁶

References

1. FDA approves first in class targeted therapy for metastatic pancreatic cancer. FDA. August 26, 2026. Accessed September 24, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-class-targeted-therapy-metastatic-pancreatic-cancer
2. 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. Presented at: 2026 ASCO Annual Meeting; May 29-June 2, 2026; Chicago, IL.
3. FDA approves zanidatamab-hrii and tislelizumab-jsgr for HER2-positive gastric, gastroesophageal junction, or esophageal adenocarcinoma. FDA. August 25, 2026. Accessed September 24, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-zanidatamab-hrii-and-tislelizumab-jsgr-her2-positive-gastric-gastroesophageal-junction
4. Shitara K, Elimova E, Liu T, et al; HERIZON-GEA-01 Investigators. Zanidatamab with and without tislelizumab in HER2-positive gastroesophageal cancer. N Engl J Med. 2026;394(20):2002-2014. doi:10.1056/NEJMoa2517729
5. ITM receives complete response letter for ¹⁷⁷Lu-edotreotide (ITM-11). News release. ITM. August 10, 2026. Accessed September 24, 2026. https://www.itm-radiopharma.com/news/press-releases/press-releases-detail/itm-receives-complete-response-letter-for-177lu-edotreotide-itm-11-763/
6. Walter T, Jann H, Ansquer C, et al. [177Lu]Lu-edotreotide versus everolimus for gastroenteropancreatic neuroendocrine tumours (COMPETE): a phase 3, multicentre, randomised, open-label, superiority trial. Lancet. 2026;408(10551):234-247. doi:10.1016/S0140-6736(26)00604-5
7. Jemperli (dostarlimab) accepted for priority review by the US FDA for dMMR/MSI-H locally advanced rectal cancer. News release. GSK. August 24, 2026. Accessed September 24, 2026. https://www.gsk.com/en-gb/media/press-releases/jemperli-dostarlimab-accepted-for-priority-review-by-the-us-fda/
8. Cercek A, Bachet JB, Capdevila J, et al. A phase two, single-arm, open-label study with dostarlimab monotherapy in participants with untreated stage II/III dMMR/MSI-H locally advanced rectal cancer (AZUR-1). Clin Colorectal Cancer. 2025;24(2):325-330. doi:10.1016/j.clcc.2025.02.003
9. Lilly’s olomorasib receives U.S. FDA’s Breakthrough Therapy designation for the treatment of previously treated KRAS G12C-mutant advanced pancreatic cancer. News release. Eli Lilly and Company. August 3, 2026. Accessed September 24, 2026. https://www.prnewswire.com/news-releases/lillys-olomorasib-receives-us-fdas-breakthrough-therapy-designation-for-the-treatment-of-previously-treated-kras-g12c-mutant-advanced-pancreatic-cancer-302840337.html
10. Study of LY3537982 in cancer patients with a specific genetic mutation (KRAS G12C). ClinicalTrials.gov. Updated May 29, 2026. Accessed September 24, 2026. https://clinicaltrials.gov/study/NCT04956640
11. Erasca granted FDA fast track designation for pan-RAS molecular glue ERAS-0015 in patients with metastatic pancreatic adenocarcinoma. News release. Erasca, Inc. August 24, 2026. Accessed September 24, 2026. https://investors.erasca.com/news-releases/news-release-details/erasca-granted-fda-fast-track-designation-pan-ras-molecular-glue
12. SYS6090 (JMT108) granted fast track designation by U.S. FDA for treatment of patients with MSS/pMMR mCRC. News release. CSPC Pharmaceutical Group Limited. August 26, 2026. Accessed September 24, 2026. https://doc.irasia.com/listco/hk/cspc/announcement/a260826a.pdf
13. A phase Ib/II study of SYS6090 combination therapy in advanced colorectal cancer. ClinicalTrials.gov. Updated August 6, 2026. Accessed September 24, 2026. https://clinicaltrials.gov/study/NCT07750041
14. CytomX Therapeutics announces FDA fast track designation for varsetatug masetecan (“Varseta-M”) for relapsed/refractory metastatic colorectal cancer (R/R mCRC). News release. CytomX Therapeutics. August 27, 2026. Accessed September 24, 2026. https://ir.cytomx.com/news-releases/news-release-details/cytomx-therapeutics-announces-fda-fast-track-designation
15. CytomX’s varsetatug masetecan (EpCAM PROBODY ADC) continues to demonstrate positive data supporting potential as a new treatment option in late-line colorectal cancer. News release. CytomX Therapeutics. March 16, 2026. Accessed September 24, 2026. https://ir.cytomx.com/news-releases/news-release-details/cytomxs-varsetatug-masetecan-epcam-probodyr-adc-continues
16. Pliant Therapeutics receives FDA fast track designation for PLN-101095 in combination with pembrolizumab for the treatment of ICI-refractory solid tumors. News release. Pliant Therapeutics. August 18, 2026. Accessed September 24, 2026. https://ir.pliantrx.com/news-releases/news-release-details/pliant-therapeutics-receives-fda-fast-track-designation-pln-1
17. Pliant Therapeutics announces interim data from PLN-101095 in patients with immune checkpoint inhibitor-refractory advanced solid tumors. News release. Pliant Therapeutics. December 4, 2025. Accessed September 24, 2026. https://ir.pliantrx.com/news-releases/news-release-details/pliant-therapeutics-announces-interim-data-pln-101095-patients