Decoding Key Community Oncology Takeaways From ASCO GI 2026

In the latest episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS; and Benjamin Garmezy, MD, convened with Meredith Pelster, MD, MSCI; and Jason Henry, MD. Together, they looked back at the presentations and data shared at the 2026 ASCO Gastrointestinal Cancers Symposium that may have long-term impacts on community oncology practice across different gastrointestinal (GI) malignancies, including pancreatic cancer and colorectal cancer (CRC).

Trials and sessions of interest included the following:

1. Phase 1 Trial (NCT06179160) of INCB161734¹
   1. INCB161734, an investigational KRAS G12D small molecule inhibitor, displayed a manageable safety profile among patients with advanced or metastatic pancreatic ductal adenocarcinoma.
   2. The agent produced a disease control rate of 73% (n = 16/22) given at 600 mg once daily and 86% (n = 25/29) when given at 1200 mg once daily.
2. Phase 3 BREAKWATER Trial (NCT04607421)²
   1. Among those with BRAF V600E-mutated metastatic CRC, encorafenib (Braftovi) plus cetuximab (Erbitux) and chemotherapy improved the overall response rate (ORR) at 64.4% vs 39.2% with chemotherapy with or without bevacizumab (Avastin) in the control arm (OR, 2.76; 95% CI, 1.42-5.35; P = .001).
   2. Overall, the data supported the encorafenib-based combination as a new potential standard of care in BRAF V600E-mutated metastatic CRC.
   3. The FDA recently granted traditional approval to the encorafenib regimen based on data from the BREAKWATER trial.³
3. Phase 3 COMMIT Trial (NCT02997228)⁴
   1. Chemotherapy in combination with bevacizumab and atezolizumab (Tecentriq) improved outcomes among patients with mismatch repair deficient (dMMR) or microsatellite instability–high (MSI-H) metastatic CRC vs atezolizumab alone.
   2. Data showed a median progression-free survival (PFS) of 30.0 months vs 4.3 months in the combination and monotherapy arms, respectively.

Bupathi is the executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and a medical oncologist with Rocky Mountain Cancer Centers, specializing in solid tumors and genitourinary cancers. Garmezy is the associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and a medical oncologist at SCRI Oncology Partners, specializing in genitourinary cancers.

Pelster is associate director of GI Cancer Research at SCRI Oncology Partners and specializes in treating GI cancers as well as head and neck cancers. Henry is associate director of Drug Development at Sarah Cannon.

References

1. Wainberg ZA, Henry JT, Park H, et al. Preliminary phase 1 results of INCB161734, a novel oral Kirsten rat sarcoma (KRAS) G12D inhibitor, as monotherapy or in combination with chemotherapy for advanced/metastatic pancreatic duct adenocarcinoma (PDAC). J Clin Oncol. 2026;44(suppl 2):654. doi:10.1200/JCO.2026.44.2_suppl.654
2. Kopetz S, Wasan HS, Yoshino HS, et al. BREAKWATER: primary analysis of first-line (1L) encorafenib + cetuximab (EC) + FOLFIRI in BRAF V600E-mutant metastatic colorectal cancer (mCRC). J Clin Oncol. 2026;44(suppl 2):13. doi:10.1200/JCO.2026.44.2_suppl.13
3. FDA grants traditional approval to encorafenib for metastatic colorectal cancer with a BRAF V600E mutation. News release. FDA. February 24, 2026. Accessed February 25, 2026. https://tinyurl.com/4xr84a6y
4. Rocha Lima CMS, Yothers G, George TJ, et al. Colorectal Cancer Metastatic dMMR Immunotherapy (COMMIT) study: a randomized phase III study of atezolizumab (atezo) monotherapy versus mFOLFOX6/bevacizumab/atezo (FFX/bev) in the first-line treatment of patients (pts) with deficient DNA mismatch repair (dMMR) or microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC)— NRG-GI004/SWOG-S1610. J Clin Oncol. 2026;44(suppl 2):14. doi:10.1200/JCO.2026.44.2_suppl.14