Suvemcitug Combination Therapy Exhibits Safety, Activity in MSS/pMMR CRC

In a small cohort of patients with MMS/pMMR CRC, the suvemcitug and envafolimab pharmacokinetic profiles were comparable with prior monotherapy studies.

Suvemcitug (BD0801) plus envafolimab (KN035) with leucovorin calcium, fluorouracil, and irinotecan hydrochloride (FOLFIRI), exhibited a manageable safety profile and preliminary anti-tumor activity in adult patients with microsatellite–stable or mismatch repair–proficient (MSS/pMMR) colorectal cancer (CRC) in the second-line setting in which one prior line of therapy had failed them, according to findings from a single small cohort of a non-randomized prospective phase 2 study (NCT05148195) published in the International Journal of Colorectal Disease.¹

Data from the study showed that among patients with MSS/pMMR CRC treated with the combination regimen (n = 20), the confirmed objective response rate (ORR) was 25.0% (95% CI, 8.66%-49.10%), with 17 patients experiencing tumor reduction in target lesions, 8 of whom the reduction was 30% or greater. Additionally, 3 patients achieved unconfirmed partial responses.

Among those with KRAS mutation, the ORR was 16.7% (95% CI, 0.42%-64.12%). Additionally, the ORR was 27.3% (95% CI, 6.02%-60.97%) in those with liver metastases and 36.4% (95% CI, 10.93%-69.21%) in those with lung metastases. Among patients who received 1 prior line of therapy, the ORR was 33.3% (95% CI, 11.82%-61.62%); in those who received 1 prior line of antiangiogenic therapy, it was 20.0% (95% CI, 2.52%-55.61%).

“The pharmacokinetic and immunogenicity results in this current study indicated that the [pharmacokinetic and anti-drug antibody] profiles of suvemcitug and envafolimab were comparable with the previous monotherapy studies,” Ying Liu, MD, of the Department of Internal Medicine at Changchun University of Science and Technology and Jilin Cancer Hospital, wrote in the publication with study coinvestigators.¹ “Furthermore, the incidence and duration of positive immunogenicity responses were generally deemed safe and manageable.”

Between December 17, 2021, and August 10, 2023, patients with MSS/pMMR CRC were enrolled to receive suvemcitug plus envafolimab and FOLFIRI. Treatment with suvemcitug began at 2 mg/kg biweekly during the safety run-in stage, with dose expansion occurring after the recommended dose was confirmed.

Patients on trial received 200 mg of intravenous envafolimab biweekly. Following envafolimab treatment, patients received the intravenous infusion of FOLFIRI, containing 180 mg/m² of irinotecan, 200 mg/m² of leucovorin or 400 mg/m² of leucovorin, and a 5-fluorouracil 400 mg/m² bolus and continuous 2400 mg/m². Treatment continued for 6 to 8 two-week cycles, and all patients were treated until unacceptable toxicity or disease progression.

Patients included on the trial had a median age of 56.0 years, with 30% of patients older than 65 years. A total of 60% of patients were male, 75% had left-sided or rectal tumors, and 90% had an ECOG performance status score of 1.

Additionally, 40% and 30% of patients had KRAS wild-type or were KRAS-mutant, 55% had lung metastases, and 55% had liver metastases. A total of 75% of patients had 1 prior line of therapy, 50% had previous antiangiogenic therapy, and 90% did not have previous anti-EGFR antibody therapy.

The primary end points were the recommended dose. Secondary end points included duration of response, progression-free survival, disease control rate, overall survival, and safety.²

No dose-limiting toxicities were observed in the safety run-in cohort (n = 6). Any-grade treatment-related adverse effects (TRAEs) occurred in all 20 patients evaluable for safety. Additionally, grade 3 or higher TRAEs were observed in 90% of patients and 35% of patients experienced serious TRAEs. No TRAEs that were fatal were reported.

The most common grade 3 or higher TRAEs included neutrophil count decrease (60%), hypertension (25%), and white blood cell count decrease (25%). Furthermore, the most common serious TRAEs included neutrophil count decrease (15%) and diarrhea (10%). A total of 80% of patients experienced dose interruptions, 70% experienced dose reductions, and no treatment-emergent AE-related discontinuations were reported.

References

1. Liu Y, Wang J, Fang Y, et al. The efficacy and safety of suvemcitug, envafolimab, and FOLFIRI in microsatellite-stable or mismatch repair–proficient colorectal cancer: preliminary results of a phase 2 study. Int J Colorectal Dis. 2025;40(20). doi:10.1007/s00384-025-04806-z
2. A Phase II study of envofolimab and BD0801 with/​without chemotherapy in patients with advanced solid tumors. ClinicalTrials.gov. Updated March 13, 2024. Accessed February 20, 2025. https://tinyurl.com/3fzy363j