FDA Grants Fast Track Designation to BBO-11818 in KRAS-Mutant PDAC

The FDA has granted fast track designation to the investigational pan-KRAS inhibitor BBO-11818 for adult patients with advanced KRAS-mutant pancreatic ductal adenocarcinoma (PDAC).¹

BBO-11818 is being evaluated in the phase 1 KONQUER-101 trial (NCT06917079) in heavily pretreated patients with locally advanced unresectable or metastatic KRAS-mutant solid tumors. The latest data update in December 2025 showed that BBO-11818 elicited promising antitumor activity, including a partial response in a patient with PDAC who had a 56% reduction in tumor size.² Safety across tumor types available at the time of the analysis showed that BBO-11818 monotherapy seemed to be well tolerated; no dose-limiting toxicities occurred and treatment-related adverse events were generally gastrointestinal-related.²

BridgeBio Oncology Therapeutics, the developer of BBO-11818, reported in a news release that updated results from the KONQUER-101 trial are expected to be available in the second half of 2026.¹

“Receiving fast track designation from the FDA for BBO-11818 in KRAS-mutant pancreatic ductal adenocarcinoma reflects the importance and urgency of accelerating the development of our pan-KRAS inhibitor in this serious disease,” said Yong Ben, MD, chief medical and development officer of BridgeBio Oncology Therapeutics, in the news release. “This designation will help us collaborate closely with the FDA to advance BBO-11818 as efficiently as possible for patients who need new options.”¹

Phase 1 KONQUER-101 trial

The KONQUER-101 trial is a phase 1, open-label study being conducted across multiple sites to assess how BBO-11818, a pan-KRAS inhibitor, performs as monotherapy and alongside several combination regimens—including pembrolizumab (Keytruda) with or without platinum-based chemotherapy and pemetrexed, cetuximab with or without FOLFOX, NALIRIFOX, or gemcitabine plus nab-paclitaxel—in patients with locally advanced unresectable or metastatic KRAS-mutant solid tumors.³ The trial is structured in two parts, beginning with dose escalation followed by dose expansion.

Patients are eligible to enroll if they have histologically confirmed locally advanced and unresectable or metastatic non–small cell lung cancer, PDAC, colorectal cancer or other solid tumor with KRAS G12A, G12C, G12D, G12S, or G12V mutations. They must also have measurable disease by  RECIST v1.1 criteria and an ECOG performance status of 0 to 1.³ 

The study is being conducted at 11 clinical sites in the United States. The targeted enrollment is nearly 400 patients and the estimated primary study completion date is August 2027.

Patients enrolled in the trial have received dose levels ranging from 50 mg to 800 mg on a schedule of twice daily. Researchers are currently conducting monotherapy dose escalation with monotherapy expansion and combination cohorts launching next.³ 

Rationale for Developing BBO-11818

Explaining the rationale for exploring BBO-11818, BridgeBio, wrote in this news release that despite the clinical progress made with KRAS G12C-targeted agents, the majority of KRAS-driven cancers  remain without effective targeted therapies, representing a substantial unmet need.¹ Accordingly, BBO-11818 functions as a potent pan-KRAS inhibitor capable of suppressing KRAS activity in both its active (ON) and inactive (OFF) conformational states, while maintaining high selectivity for mutant KRAS over the closely related GTPases HRAS and NRAS, added BridgeBio.¹ 

And specifically for patients with pancreatic cancer, the early efficacy signal of BBO-11818 in a heavily pretreated PDAC patient in KONQUER-101 is highly welcome, as the prognosis for these patients is poor.  The prognosis for heavily pretreated PDAC patients is poor and represents one of the most challenging clinical situations in oncology. The median overall survival in advanced PDAC is less than 12 months with first-line treatment for metastatic disease and OS is typically only a few weeks to a few months when patients progress to the third line setting and beyond with not established standard of care.⁴ 

REFERENCES

1. Boundless Bio, Inc. Boundless Bio granted US FDA fast track designation to BBO-11818 for the treatment of patients with advanced KRAS mutant cancers. News release. Published April 2, 2026. Accessed April 21, 2026. https://tinyurl.com/4zh7nfap

2. BridgeBio Oncology Therapeutics, Inc. BBOT announces new clinical data advancing its portfolio of three innovative and differentiated RAS and PI3Kα pipeline programs. Published January 7, 2026. Accessed April 21, 2026. https://tinyurl.com/zwswx3293.

3. A phase 1a/1b open-label study evaluating the safety, tolerability, pharmacokinetics, and efficacy of BBO-11818 in subjects with advanced KRAS mutant cancers (NCT06917079). Updated March 23, 2026. Accessed April 21, 2026. https://clinicaltrials.gov/study/NCT06917079.

4. Evrard C, Pelras A, Rivet S, et al. Predictive and prognostic factors of efficacy of third-line chemotherapy in patients with unresectable pancreatic cancer: a cohort-based study. Oncologist. 2025;30(6):oyaf125. doi:10.1093/oncolo/oyaf125