Adding the subcutaneous PD-L1 blocker envafolimab to short-course radiotherapy and CAPEOX (capecitabine and oxaliplatin) improved pathologic complete response (pCR) without a clear safety or surgical feasibility penalty in patients with microsatellite-stable (MSS) locally advanced rectal cancer, according to an interim analysis of the randomized phase III PRECAM-R trial.¹

The study, presented at the 2026 ASCO Breakthrough Meeting by Yiming Lv, MD, of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, China, tested whether short-course radiotherapy and chemotherapy could help prime microsatellite-stable tumors for PD-L1 blockade.

“What is supported now is improved pCR with envafolimab added to [short-course radiotherapy]/CAPEOX, with no clear safety or surgical feasibility penalty,” Dr. Lv said. He emphasized that the findings should not yet be interpreted as a survival or organ-preservation claim.

Microsatellite-stable rectal cancer is generally resistant to checkpoint inhibition, and immunotherapy alone has limited activity in most microsatellite-stable tumors. The rationale for PRECAM-R was that short-course radiotherapy might create an immune-priming window, allowing chemotherapy and PD-L1 blockade to deepen pathologic response before surgery.

A Compact Neoadjuvant Strategy

PRECAM-R enrolled patients with resectable stage II to III microsatellite-stable locally advanced rectal cancer, including cT3–4a or node-positive disease. Patients were randomly assigned to receive short-course radiotherapy at 5 × 5 Gy followed by two cycles of CAPEOX plus subcutaneous envafolimab, or the same short-course radiotherapy and CAPEOX backbone without PD-L1 blockade.

Total mesorectal excision was performed after neoadjuvant therapy. The primary endpoint was pathologic complete response, defined as ypT0N0. Secondary endpoints included tumor regression grade, major pathologic response, neoadjuvant rectal score, and safety. The prespecified interim analysis was triggered after 58 eligible patients completed surgery, with 29 patients in each arm.

Baseline characteristics were well balanced between the two groups, and 77.6% of patients had stage III disease.

Dr. Lv described the goal as intensifying immune pressure within a short neoadjuvant pathway without extending treatment or making surgery more difficult.

Pathologic Response Improved

The main finding was a higher pathologic complete response rate with envafolimab plus short-course radiotherapy/CAPEOX: 44.8% vs 13.8% with short-course radiotherapy/CAPEOX alone (P = .0195).

Major pathologic response, defined as tumor regression grade 0 or 1, was also numerically higher with envafolimab plus short-course radiotherapy/CAPEOX (72.4% vs 51.7%), although the difference was not statistically significant. Neoadjuvant rectal score distribution also favored the experimental arm (P = .036), with Dr. Lv noting that lower scores indicate better prognosis.

No early distant metastases were reported in the experimental arm; distant metastases were reported in four patients in the control arm, including two liver events and two lymph node events after surgery. Dr. Lv cautioned that this exploratory finding should not be interpreted as a disease-free survival benefit.

Safety and Surgical Feasibility

The addition of envafolimab did not appear to compromise safety or surgery in the interim cohort. Grade 3 or 4 adverse events were uncommon. Any adverse event occurred in 72.4% of patients in the experimental arm and 65.5% of those in the control arm, and immune-related adverse events were uncommon. Postoperative complications occurred in 10.3% of patients in the experimental arm and 13.8% of those in the control arm, and surgical metrics were comparable between groups.

Dr. Lv said the gain in pathologic response did not come with a clear toxicity or surgical feasibility penalty. Still, he noted that disease-free survival is immature, durability needs longer follow-up, and organ preservation has not been established by this dataset.

He said the interim data support continued evaluation of short-course radiotherapy/CAPEOX plus envafolimab as a promising strategy in microsatellite-stable locally advanced rectal cancer.

Discussant Perspective

Formal discussant Ho Gwo Fuang, FRCR, MRCP, MBChP, BSc, of University of Malaya Medical Centre, placed PRECAM-R in the broader context of efforts to make microsatellite-stable rectal cancer more responsive to immunotherapy.

Ho Gwo Fuang, FRCR, MRCP, MBChP, BSc

Most rectal cancers are microsatellite-stable, Dr. Fuang noted, and these tumors are generally resistant to immune checkpoint inhibitors because of low neoantigen burden, immune exclusion, and suppressive myeloid cells. Radiotherapy may help alter that biology by inducing immunogenic cell death, increasing antigen presentation, and releasing tumor neoantigens—an “in-situ vaccination effect” that may prime tumors for checkpoint inhibition, he said.

Against that background, Dr. Fuang said PRECAM-R stands out because it is a randomized phase III study with a proper control arm. He highlighted the 44.8% pathologic complete response rate with envafolimab plus short-course radiotherapy/CAPEOX, as well as the numerically higher major pathologic response rate.

He described the regimen as potentially practice-changing, but not definitive. Strengths include the randomized design, the unmet need in microsatellite-stable locally advanced rectal cancer, the convenience of a short-course platform, and the use of only 5 days of radiotherapy and two cycles of chemotherapy plus PD-L1 blockade.

However, he emphasized several reasons for caution: the interim dataset included only 58 patients, pathologic complete response is a surrogate endpoint, and the effect size may change as data mature. More mature data are needed for disease-free survival, overall survival, and organ-preservation outcomes, he said. 

DISCLOSURE: Dr. Lv reported no conflicts of interest. Dr. Fuang reported consulting or advisory roles with Amgen, Astellas Pharma, AstraZeneca, Boehringer Ingelheim, MSD, Novartis, Pfizer, Roche, and Takeda; speakers bureau participation with AstraZeneca, Boehringer Ingelheim, Eisai, Gene Solutions, Merck, MSD, Novartis, Pfizer, and Roche; and travel, accommodations, or expenses from AstraZeneca, Bristol Myers Squibb, Ipsen, Merck Serono, MSD Oncology, Pfizer, Regeneron, SERVIER, and Zuellig Pharma.

REFERENCE

1. Lv Y, Wang F,et al: Short-course radiotherapy and chemotherapy with or without PD-L1 blockade (envafolimab) for MSS locally advanced rectal cancer: 2026 ASCO Breakthrough Meeting. Abstract 92. Presented June 25, 2026.