FDA Flashback: GI Cancer Decisions and News From July 2026

Catch a glimpse of the gastrointestinal (GI) cancer–related FDA decisions and announcements from July 2026, including the acceptance of a new drug application (NDA) for an oral RAS(ON) multiselective inhibitor in pretreated metastatic pancreatic cancer, the approval of a blood-based colorectal cancer (CRC) screening test, the granting of tentative approval to a bioequivalent formulation of olaparib, a third complete response letter (CRL) for a combination in first-line hepatocellular carcinoma (HCC), 2 fast track designations, and the finalization of 3 guidance documents intended to broaden eligibility for oncology clinical trials.

What is the significance of the FDA acceptance of the NDA for daraxonrasib in previously treated metastatic pancreatic cancer?

On July 22, 2026, the FDA accepted an NDA seeking the approval of daraxonrasib (RMC-6236), an oral RAS(ON) multiselective inhibitor, for the treatment of adult patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC).¹ The agent was selected for the FDA Commissioner’s National Priority Voucher pilot program, which aims to accelerate the review of medicines addressing key national health priorities. Daraxonrasib previously received FDA breakthrough therapy and orphan drug designations in this setting.

The NDA was supported by data from the global, randomized phase 3 RASolute 302 trial (NCT06625320), which enrolled patients with previously treated metastatic PDAC and met its dual primary end points of overall survival (OS) and progression-free survival (PFS) in the population of patients with RAS G12–mutant disease.^1,2 At an analysis presented at the 2026 ASCO Annual Meeting, patients who received daraxonrasib (n = 228) achieved a median OS of 13.2 months (95% CI, 10.0-not estimable) vs 6.6 months (95% CI, 5.4-8.2) among those given investigator’s choice of chemotherapy (n = 231; HR, 0.40; 95% CI, 0.30-0.54; P < 5.9×10^⁻¹⁰).² The median PFS by blinded independent central review was 7.3 months (95% CI, 6.3-8.1) with daraxonrasib 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).

What is important to note about the FDA approval of the SimpleScreen CRC blood-based screening test?

On July 27, 2026, the FDA approved SimpleScreen CRC, a blood-based screening test for CRC, for use in adults 45 years and older who are at average risk for the disease and have been referred for screening by a health care provider.³ With approval, the test meets Medicare coverage criteria and is expected to be incorporated into American Cancer Society screening guidelines.

The approval was supported by data from the PREEMPT CRC trial (NCT04369053), a prospective validation study that enrolled more than 48,000 asymptomatic, average-risk adults 45 to 85 years across more than 200 United States (US) sites, all of whom were scheduled for a screening colonoscopy. In a prespecified analysis adjusted to match the US Census, SimpleScreen CRC detected CRC at a sensitivity rate of 81.1% and advanced precancerous lesions (APLs) at a sensitivity rate of 13.7%, including a 30.7% sensitivity rate for APLs with high-grade dysplasia. The test demonstrated a 90.4% specificity rate for advanced colorectal neoplasia.

What is the regulatory status of bioequivalent olaparib?

On July 20, 2026, a bioequivalent formulation of olaparib received FDA tentative approval for use across the previously approved indications of the reference product, olaparib (Lynparza).⁴ The tentative approval was granted for generic olaparib tablets in 100-mg and 150-mg strengths.

Olaparib is a PARP inhibitor with indications spanning several tumor types. Among GI cancers, olaparib is approved for the first-line maintenance treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen.⁵

What is the regulatory status of rivoceranib plus camrelizumab in first-line HCC?

On July 10, 2026, the FDA issued a third CRL for the combination of rivoceranib, an oral TKI, and camrelizumab, an anti–PD-1 antibody, as a first-line treatment for patients with unresectable or metastatic HCC.⁶ The CRL cited deficiencies identified during a current Good Manufacturing Practice inspection of a manufacturing site listed on the rivoceranib NDA.

The NDA was supported by data from the phase 3 CARES-310 trial (NCT03764293), which randomly assigned 543 systemic therapy–naive patients with unresectable HCC 1:1 to receive camrelizumab plus rivoceranib or sorafenib (Nexavar) monotherapy.^6,7 The combination produced a median OS of 23.8 months (95% CI, 20.6–27.2) vs 15.2 months (95% CI, 13.2–18.5) with sorafenib (HR, 0.64; 95% CI, 0.52-0.79; P < .0001), as well as a median PFS of 5.6 months (95% CI, 5.5-7.4) vs 3.7 months (95% CI, 3.1-3.7), respectively (HR, 0.54; 95% CI, 0.44-0.67; P < .0001).⁷

What is the regulatory status of SOT109 in advanced colorectal cancer?

On July 14, 2026, the FDA granted fast track designation to SOT109, a CDH17-targeting antibody-drug conjugate (ADC), for the treatment of patients with advanced unresectable or metastatic CRC who have exhausted standard treatment options.⁸ SOT109 targets CDH17, an antigen expressed in approximately 90% of CRC cases. A first-in-human phase 1/2 trial of SOT109 in patients with advanced unresectable or metastatic CRC is expected to be initiated in the third quarter of 2026.

What is the regulatory status of pelareorep in pretreated squamous cell carcinoma of the anal canal?

On July 20, 2026, the FDA granted fast track designation to pelareorep in combination with a checkpoint inhibitor for the treatment of patients with inoperable, locally recurrent, or metastatic squamous cell carcinoma of the anal canal (SCAC) who have progressed on or are intolerant to 1 or more prior lines of systemic therapy.⁹ The designation was supported by efficacy data from the phase 1/2 GOBLET trial (NCT07280377), in which pelareorep plus a checkpoint inhibitor was evaluated in patients with advanced SCAC whose disease had progressed following prior therapy. The combination produced an objective response rate of 30% (n = 6/20), including durable complete responses in 2 patients, with a median duration of response of 15.5 months.¹⁰

What guidance did the FDA finalize regarding cancer clinical trial eligibility criteria?

On July 27, 2026, the FDA’s Oncology Center of Excellence issued 3 final guidance documents intended to broaden eligibility criteria for participation in clinical trials evaluating oncology drugs, with the documents addressing performance status, washout periods and concomitant medications, and laboratory values.^11,12,13,14 Each document finalizes a draft first issued in April 2024. According to the FDA, fewer than 5% of patients with cancer who are currently receiving treatment are enrolled in clinical trials, despite more than 70% reporting that they are willing to participate.¹¹ The guidances aim to address the stringent and complex eligibility criteria that are barriers to enrollment.

The performance status guidance recommends expanding criteria to include patients across a wider range of performance status and outlines alternative trial designs, such as prespecified cohorts for patients with a lower performance status.¹² The washout periods and concomitant medications guidance encourages sponsors to evaluate whether time-based washout periods are necessary for a given study and makes some allowances for patients who are receiving other medications.¹³ The laboratory values guidance calls for a more scientific, safety-focused approach to the test thresholds used to determine eligibility.¹⁴

References

1. Revolution Medicines’ new drug application for daraxonrasib accepted for review by US FDA for previously treated metastatic pancreatic cancer. News release. Revolution Medicines, Inc. July 22, 2026. Accessed August 10, 2026. https://ir.revmed.com/news-releases/news-release-details/revolution-medicines-new-drug-application-daraxonrasib-accepted
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 Freenome's SimpleScreen CRC blood-based screening test; Abbott to commercialize in the US. News release. Freenome, Inc. July 27, 2026. Accessed August 10, 2026. https://www.freenome.com/newsroom/fda-approves-freenomes-simplescreen-crc/
4. NATCO receives tentative approval for olaparib tablets from the United States Food and Drug Administration (U.S. FDA). News release. NATCO Pharma. July 20, 2026. Accessed August 10, 2026. https://www.natcopharma.co.in/insights/news-and-announcements
5. Lynparza. Prescribing information. AstraZeneca; July 2025. Accessed August 6, 2026. https://drd9vrdh9yh09.cloudfront.net/50fd68b9-106b-4550-b5d0-12b045f8b184/00997c3f-5912-486f-a7db-930b4639cd51/00997c3f-5912-486f-a7db-930b4639cd51_viewable_rendition__v.pdf
6. Elevar Therapeutics receives FDA complete response letter for combination of rivoceranib and camrelizumab as a first-line treatment for unresectable or metastatic hepatocellular carcinoma. News release. Elevar Therapeutics, Inc. July 10, 2026. Accessed August 10, 2026. https://www.biospace.com/press-releases/elevar-therapeutics-receives-fda-complete-response-letter-for-combination-of-rivoceranib-and-camrelizumab-as-a-first-line-treatment-for-unresectable-or-metastatic-hepatocellular-carcinoma
7. Qin S, Gu S, Chan SL, et al; CARES-310 Study Group. Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): final analysis of a randomised, open-label, international, phase 3 study. Lancet Oncol. 2025;26(12):1598-1611. doi:10.1016/S1470-2045(25)00543-1
8. FDA grants fast track designation to SOTIO’s SOT109, a CDH17-targeting ADC for colorectal cancer. News release. SOTIO Biotech. July 14, 2026. Accessed August 10, 2026. https://www.globenewswire.com/news-release/2026/07/14/3326803/0/en/fda-grants-fast-track-designation-to-sotio-s-sot109-a-cdh17-targeting-adc-for-colorectal-cancer.html
9. Oncolytics Biotech receives fast track designation for pelareorep in second-line and later anal cancer. News release. Oncolytics Biotech Inc. July 20, 2026. Accessed August 10, 2026. https://www.globenewswire.com/news-release/2026/07/20/3329774/0/en/Oncolytics-Biotech-Receives-Fast-Track-Designation-for-Pelareorep-in-Second-Line-and-Later-Anal-Cancer.html
10. Oncolytics Biotech reports updated anal cancer data showing objective response rate more than double the current standard of care. News release. Oncolytics Biotech. October 28, 2025. Accessed August 10, 2026. https://ir.oncolyticsbiotech.com/press_releases/oncolytics-biotech-reports-updated-anal-cancer-data-showing-objective-response-rate-more-than-double-the-current-standard-of-care/
11. Final guidances to expand participation in cancer clinical trials. FDA Oncology Center of Excellence. July 2026. Accessed July 27, 2026. https://www.fda.gov/about-fda/oncology-center-excellence/oncology-center-excellence-guidance-documents
12. Cancer clinical trial eligibility criteria: performance status. FDA. July 27, 2026. Accessed July 27, 2026. https://www.fda.gov/media/178018/download
13. Cancer clinical trial eligibility criteria: washout periods and concomitant medications. FDA. July 27, 2026. Accessed July 27, 2026. https://www.fda.gov/media/178016/download
14. Cancer clinical trial eligibility criteria: laboratory values. FDA. July 27, 2026. Accessed July 27, 2026. https://www.fda.gov/media/178013/download