A novel triple combination therapy has shown promising early efficacy for patients with microsatellite stable/mismatch repair–proficient (MSS/pMMR) colorectal cancer, according to new phase 2 trial results published in the International Journal of Colorectal Disease.
The combination regimen, consisting of envafolimab (KN035), suvemcitug, and FOLFIRI (5-fluorouracil, leucovorin, and irinotecan), demonstrated significant antitumor activity in second-line treatment. Among the 20 patients enrolled in the trial (NCT05148195), investigators observed an objective response rate (ORR) of 25.0% (95% CI, 8.66%-49.10%) and an impressive disease control rate (DCR) of 90.0% (95% CI, 68.30%-98.77%).
Efficacy and Survival Outcomes
The treatment demonstrated meaningful clinical benefit with a median progression-free survival (PFS) of 5.6 months (95% CI, 4.01-8.25) and a median duration of response (DOR) of 4.1 months (95% CI, 3.02-not evaluable). Notably, patients with lung metastases showed particularly encouraging results, achieving an ORR of 36.4% (95% CI, 10.93%-69.21%).
Treatment Administration and Patient Population
Patients received subcutaneous envafolimab at 200 mg every two weeks, combined with suvemcitug at 2 mg/kg every two weeks and standard FOLFIRI chemotherapy. The study population primarily consisted of patients aged 56 years (median), with 75% having left-sided or rectal tumors and 90% having an ECOG performance status of 1.
Safety Profile and Tolerability
The safety profile, while requiring careful management, proved controllable. All patients experienced treatment-related adverse effects (TRAEs), with 90% experiencing grade 3 or higher events. The most frequent severe adverse effects included:
- Decreased neutrophil count (60.0%)
- Decreased white blood cell count (25.0%)
- Hypertension (25.0%)
- Decreased lymphocyte count (15.0%)
- Oral mucositis (15.0%)
Despite the high rate of adverse events, no patients discontinued treatment due to toxicity, though dose modifications were common. Approximately 80% of patients required dose interruptions, and 70% needed dose reductions.
Clinical Implications
The study represents a significant step forward in addressing the treatment needs of MSS/pMMR colorectal cancer patients who have progressed after first-line therapy. The combination builds upon previous research showing efficacy of suvemcitug plus FOLFIRI in advanced CRC, with the addition of envafolimab potentially enhancing therapeutic outcomes.
Envafolimab's role in this combination is particularly noteworthy, as it is a unique single-domain anti–PD-L1 antibody designed for subcutaneous administration. The agent has already received approval in China for treating microsatellite instability–high/mismatch repair–deficient advanced solid tumors.
The investigators emphasized the need for additional research to identify specific patient subgroups who might derive the greatest benefit from this combination approach. These findings open new possibilities for treating a patient population that traditionally has limited therapeutic options after first-line treatment failure.
