FDA Grants Fast Track Designation to Botensilimab Plus Balstilimab for Non-MSI-H/dMMR mCRC
Key Insights
The FDA has granted Fast Track designation to botensilimab plus balstilimab for treating non-MSI-H/dMMR metastatic colorectal cancer (search) (mCRC (search)).
The designation targets heavily pretreated patients resistant or intolerant to standard therapies, including fluoropyrimidine, oxaliplatin, irinotecan, VEGF (search) inhibitors, EGFR (search) inhibitors, and BRAF (search) inhibitors.
Phase 1a/b trial data showed an overall response rate of 23% and a disease control rate of 76% in patients with microsatellite stable, refractory mCRC (search) treated with the combination.
The FDA has granted Fast Track designation to the combination of botensilimab (AGEN1181) plus balstilimab (AGEN2034) for the treatment of patients with non–microsatellite instability–high (MSI-H)/mismatch repair–deficient (dMMR) metastatic colorectal cancer (search) (mCRC (search)) with no active liver involvement. This regulatory decision aims to expedite the development and review of this therapeutic combination for a patient population with limited treatment options.
The Fast Track designation is specifically for heavily pretreated patients who have developed resistance or intolerance to fluoropyrimidine, oxaliplatin, and irinotecan. These patients have also received a VEGF (search) inhibitor, an EGFR (search) inhibitor, and/or a BRAF (search) inhibitor, if indicated, reflecting the advanced stage and aggressive nature of their disease.
Clinical Trial Data
An ongoing phase 2 trial (NCT05608044) is currently evaluating botensilimab monotherapy and its combination with balstilimab versus standard-of-care therapy in patients with unresectable mCRC (search) who have received prior chemotherapy for metastatic or recurrent disease. Furthermore, a global phase 3 trial assessing the combination in patients with non–MSI-H CRC is anticipated to commence in 2023.
Data from a phase 1a/b trial (NCT03860272) presented at the 2023 Gastrointestinal Cancers Symposium demonstrated promising results. With a median follow-up of 7 months (range, 2-31), the combination of botensilimab and balstilimab achieved an overall response rate (ORR) of 23% (95% CI, 14%-34%) in patients with microsatellite stable (MSS), refractory mCRC (search) (n = 70). The study reported one complete response (1%), 21% partial responses, and 53% stable disease, resulting in a disease control rate (DCR) of 76% (95% CI, 64%-85%).
Survival Outcomes
The median overall survival (OS) was not yet reached (NR; 95% CI, 10.3 months-NR) for the overall population, and the 12-month OS rate was 63% (95% CI, 46%-76%). In patients without active liver metastases, the median OS was NR (95% CI, NR-NR), with a 12-month OS rate of 81% (95% CI, 66%-90%). Patients with active liver metastases had a median OS of 9.4 months (95% CI, 6.1-NR) and a 12-month OS rate of 40% (95% CI, 17%-62%). The median progression-free survival (PFS) in the overall population was 4.1 months (95% CI, 2.8-5.5).
Safety Profile
Regarding safety, any-grade treatment-related adverse events (TRAEs) occurred in 64% of patients, with 40% experiencing grade 3 TRAEs and 3% grade 4 TRAEs. Common any-grade TRAEs included immune-mediated diarrhea (43%), nausea (23%), fatigue (34%), decreased appetite (27%), chills (21%), pyrexia (23%), rash (27%), pruritus (17%), and hypo/hyperthyroidism (16%).
Ongoing Investigations
Botensilimab is also under investigation in phase 2 trials for patients with advanced melanoma (search) (NCT05529316) and metastatic pancreatic cancer (search) (NCT05630183), expanding its potential therapeutic applications across various solid tumors.