Neoadjuvant Pembrolizumab in Stages I-III Deficient Mismatch Repair Colon Cancer: A Clinical Trial.

OBJECTIVE

To investigate the safety and efficacy of single-cycle pembrolizumab in patients with localized deficient mismatch repair (dMMR) colon cancer.

BACKGROUND

Neoadjuvant immunotherapy has induced remarkable rates of pathologic complete response (pCR) in patients with dMMR colon cancer. However, the optimal length and type of treatment are yet to be determined.

METHODS

This was an investigator-initiated, multicenter, single-arm, phase II study (ClinicalTrials.gov: NCT05662527) investigating the safety and efficacy of neoadjuvant pembrolizumab in patients with stage I-III dMMR colon cancer. Patients received a single cycle of pembrolizumab 4 mg/kg (maximum 400 mg) and underwent surgery 3 to 5 weeks later. An interim safety and efficacy analysis after including 42 patients was pre-planned. The primary outcomes were safety and efficacy (pCR in more than 20% of patients).

RESULTS

Between February 2023 and September 2023, 42 patients were enrolled at 5 Danish hospitals. All patients received pembrolizumab and underwent surgery, except one patient who refused to undergo surgery. Surgery was performed a median of 32 days after pembrolizumab treatment. Twenty surgical complications were observed in 16 of 41 patients (39%), 3 of which were above Clavien-Dindo grade 2. Two were grade 3b, and 1 was a surgery-related grade 5 gastric ulcer perforation. Three adverse events were grade 3. No grade 4 or 5 adverse events were reported. Of the evaluable patients, 46% (19/41) achieved a pCR, whereas 61% had a major pathologic response.

CONCLUSIONS

Neoadjuvant single-cycle pembrolizumab was well tolerated and effective in patients with localized dMMR colon cancer. Thus, the inclusion of patients was continued until 85 patients.