At the beginning of 2025, the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI) was held in San Francisco, drawing significant attention from scholars worldwide. During the event, Professor Ying Yuan from The Second Affiliated Hospital Zhejiang University School of Medicine presented new subgroup survival data from the Phase II BBCAPX study. These findings offer a promising treatment strategy for patients newly diagnosed with RAS-mutant/microsatellite-stable (MSS) unresectable metastatic colorectal cancer (mCRC) with liver metastases.Following the presentation, Professor Kefeng Ding joined Professor Yuan in a dialogue reflecting on the key progress of the study and its future direction, rekindling hope for immunotherapy in this particularly challenging mCRC subset. A summary of their conversation is presented below.
Professor Kefeng Ding: At the recent ASCO GI conference, Professor Ying Yuan from our hospital presented the latest subgroup analysis from the BBCAPX Phase II trial, which provides more detailed guidance for the treatment of RAS-mutant/MSS unresectable mCRC. This marks the fourth time the BBCAPX study has been selected for presentation at ASCO-related conferences. To begin, I would like to ask Professor Yuan to briefly review the study design and main findings.
Professor Ying Yuan: The BBCAPX study is a single-arm, open-label, Phase II clinical trial designed to investigate the efficacy and safety of first-line therapy combining the immune checkpoint inhibitor sintilimab, the anti-angiogenic agent bevacizumab, and standard doublet chemotherapy (CapeOX) in patients with RAS-mutant/MSS unresectable mCRC. The primary endpoints were objective response rate (ORR), evaluated according to RECIST 1.1, and adverse events, assessed based on CTCAE version 5.0. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).
Since 2022, this study has been selected for presentation at the ASCO Annual Meeting for three consecutive years and has garnered considerable attention. A total of 25 treatment-naïve patients with RAS-mutant/MSS mCRC were enrolled.
The latest data show that the ORR has reached 84%, and the DCR is 100%. The median PFS in the full analysis set was 17.9 months, while in the per-protocol analysis set, it was 9.79 months. The most common adverse event was neutropenia, and no grade 5 adverse events were observed.
These results represent the current efficacy and safety data achieved in the trial and highlight the therapeutic potential of this regimen in a patient group that has traditionally posed a significant challenge for immunotherapy.
Professor Kefeng Ding: At this year’s ASCO GI, you presented subgroup data focused on patients with liver metastases. Could you share how this subgroup performed in the study?
Professor Ying Yuan: At the ASCO GI meeting, we presented the subgroup analysis of patients with liver metastases from the BBCAPX study. As of the data cutoff in September 2024, among the 25 enrolled patients, 10 had liver-only metastases, while 15 had metastases involving other sites.
For patients with liver-only metastases, the median progression-free survival (mPFS) reached 25.3 months, whereas those with metastases at other sites had an mPFS of 11.5 months. The median overall survival (mOS) for the liver-only subgroup has not yet been reached, while the mOS for patients with non-liver-only metastases was 35.5 months.
Although the sample size is limited, the data suggest that patients with liver-only metastases may derive particularly strong benefit from this treatment regimen. In addition, among the 25 patients enrolled, 5 to 6 unexpectedly achieved conversion to resectability. This conversion rate is quite comparable to results reported in several previous studies.
Professor Kefeng Ding: Thank you for your insights. Mechanistically speaking, although patients with RAS-mutant/MSS mCRC are typically in an immunosuppressive state and generally have poor responses to immunotherapy, anti-angiogenic therapy may help reverse the immunosuppressive tumor microenvironment. It does so by normalizing tumor vasculature and promoting T-cell infiltration and activation. Additionally, chemotherapy may enhance tumor immunogenicity, which can synergize with immune checkpoint inhibitors.
Based on this rationale, the BBCAPX regimen offers a highly promising immunotherapy-based combination strategy for RAS-mutant/MSS unresectable mCRC, especially in patients with liver-only metastases. The combination of sintilimab with bevacizumab and CapeOX demonstrates encouraging potential. This study has important clinical implications—it shows that patients who were traditionally considered poor candidates for immunotherapy may become responsive, ultimately gaining clinical benefit.
Thank you again, Professor Yuan, for sharing these valuable updates and your clinical experience. May I ask, what are your next research plans?
Professor Ying Yuan: Building upon the encouraging efficacy and safety results from this Phase II trial, we have already launched a nationwide, Phase III, multicenter, randomized controlled trial (NCT05171660). The study targets newly diagnosed patients with unresectable RAS-mutant/MSS mCRC. Participants are randomized 1:1 to receive either sintilimab in combination with bevacizumab plus CapeOX, or bevacizumab plus CapeOX alone as first-line treatment. The primary endpoint is progression-free survival (PFS).
This trial has already been initiated across more than 20 centers nationwide, with a planned enrollment of 446 patients. We have currently enrolled nearly 400 patients, and we look forward to the early release of data, which we hope will provide robust evidence to guide immunotherapy strategies for this difficult-to-treat patient population.
Professor Kefeng Ding: We look forward to the results of this trial and hope it will provide valuable guidance for first-line treatment of RAS-mutant/MSS mCRC.
The Second Affiliated Hospital Zhejiang University School of Medicine
- Chief Physician, Doctoral Supervisor
- Lead Scientist of National “Four Major Chronic Diseases” Key R&D Project
- Lead Scientist of National 13th Five-Year Key R&D Program in Colorectal Cancer
- Deputy Party Secretary and Vice President, Zhejiang University Second Hospital
- Selected Talent in Zhejiang Province “Ten Thousand Talents Program” and recognized Medical Leader
- Distinguished Professor, Zhejiang University
- Head of Colorectal Cancer Academic Degree Program, Zhejiang University School of Medicine
- Deputy Director, Zhejiang Provincial Key Laboratory of Systemic Tumor Pharmacology and Basic Research Innovation Center (Ministry of Education); Deputy Director, Colorectal Cancer Institute of Zhejiang University School of Medicine
- Vice Chair, Colorectal Cancer Committee, Chinese Anti-Cancer Association
- Chair, NOSES Committee, Chinese Medical Doctor Association
- Chair, Colorectal Surgery Professional Committee, Chinese Research Hospital Association
- Standing Committee Member, Colorectal Cancer Branch, Chinese Society of Clinical Oncology (CSCO)
- Deputy Chair, Colorectal Cancer Committee, Zhejiang Anti-Cancer Association
- Council Member, Zhejiang Medical Association; Chair of the Colorectal Cancer Subcommittee and Precision Medicine Subcommittee
Professor Ding has led numerous national and provincial research programs, including 1 National Key R&D Project, 1 National 13th Five-Year Major Research Project, 8 National Natural Science Foundation grants, and 1 Key Project in Zhejiang’s “Leading Talents” Program. He has also led 6 major clinical trials and published over 50 SCI and core journal articles in the past five years.
Chief Physician, Professor, Doctoral Supervisor Department of Oncology,The Second Affiliated Hospital Zhejiang University School of Medicine
- Deputy Director, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education
- Executive Deputy Editor-in-Chief, Practical Oncology Journal
- Recipient of the First China Colorectal Cancer Young Scientist Award
- Winner of the Second National Top 100 Outstanding Young Role Models Award
- Council Member, Chinese Society of Clinical Oncology (CSCO)
- Deputy Chair, CSCO Colorectal Cancer Expert Committee
- Standing Committee Member, CSCO Gastric Cancer Committee
- Deputy Chair, Cancer Communication Committee, Chinese Anti-Cancer Association
- Standing Committee Member, Chemotherapy Committee, Chinese Anti-Cancer Association
- Standing Member and Head of Communication Subgroup, Colorectal Cancer Committee, Chinese Anti-Cancer Association
- Deputy Chair, Oncology Branch, Zhejiang Medical Association
- Deputy Chair, Colorectal Cancer Committee, Zhejiang Anti-Cancer Association
- Deputy Chair, Oncology Internal Medicine Committee, Zhejiang Anti-Cancer Association
