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778 Botensilimab, a novel innate/adaptive immune activator, plus or minus balstilimab (anti-PD-1) in “cold” and I-O refractory metastatic solid tumors
  1. Breelyn Wilky1,
  2. Anthony El-Khoueiry2,
  3. Andrea Bullock3,
  4. Apostolia Tsimberidou4,
  5. Daruka Mahadevan5,
  6. Kim Margolin6,
  7. Jonathan Trent7,
  8. Bruno Bockorny3,
  9. Justin Moser8,
  10. Peter Hosein7,
  11. Marwan Fakih9,
  12. Benjamin Schlecter10,
  13. Jacob Thomas2,
  14. Ani Balmanoukian11,
  15. Rachel Sanborn12,
  16. Ghassan Abou-Alfa13,
  17. Gary Schwartz14,
  18. Diana Hanna2,
  19. Waldo Ortuzar Feliu15,
  20. Joseph Grossman15,
  21. Katherine Rosenthal15,
  22. James Godwin15,
  23. Jaymin Patel15,
  24. Bonnie Bullock15,
  25. Justin Stebbing16,
  26. Bhupendra Rawal15,
  27. Hunter Cole15,
  28. Chloe Delepine15,
  29. Jacky Chow15,
  30. Ross Walker15,
  31. Chris MacDermaid15,
  32. Dhan Chand15,
  33. Michael Gordon8,
  34. Heinz-Josef Lenz2 and
  35. Steven O’Day17
  1. 1University of Colorado Cancer Center, Aurora, CO, USA
  2. 2University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA
  3. 3Beth Israel Deaconess Medical Center, Boston, MA, USA
  4. 4The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  5. 5The University of Texas Health Sciences Center at San Antonio, San Antonio, TX, USA
  6. 6Providence Saint John’s Cancer Institute, Santa Monica, CA, USA
  7. 7Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA
  8. 8HonorHealth Research and Innovation Institute, Scottsdale, AZ, USA
  9. 9City of Hope Comprehensive Cancer Center, Duarte, CA, USA
  10. 10Dana-Farber Cancer Institute, Boston, MA, USA
  11. 11The Angeles Clinic and Research Institute, Los Angeles, CA, USA
  12. 12Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA
  13. 13Memorial Sloan Kettering Cancer Center, New York, NY, USA
  14. 14Herbert Irving Comprehensive Cancer Center, Columbia University School of Medicine, New York, NY, USA
  15. 15Agenus, Lexington, MA, USA
  16. 16Agenus and Imperial College London, Lexington, MA, USA
  17. 17Agenus and Providence Saint John’s Cancer Institute*, Lexington, MA, USA


Background Botensilimab (BOT) promotes optimized T cell priming, activation and memory formation by strengthening antigen presenting cell/T cell co-engagement. As an Fc-enhanced next-generation anti-CTLA-4 antibody, BOT also promotes intratumoral Treg depletion and reduces complement fixation. We present results from patients with metastatic solid tumors treated with BOT±balstilimab (BAL; anti-PD-1) in an expanded phase IA/B study; NCT03860272.

Methods Patients received either BOT monotherapy at 0.1-3 mg/kg every 3 weeks (Q3W), BOT monotherapy 1 or 2mg/kg every 6 weeks (Q6W), BOT 0.1-2mg/kg Q6W+BAL 3 mg/kg every 2 weeks, or a fixed-dose of BOT 150mg Q6W+BAL 450mg Q3W. Unconfirmed responses are included. Of the 44 BOT monotherapy patients, 13 crossed over to combination.

Results 142 patients (98 combination, 44 monotherapy [13 crossover]) were evaluable for efficacy/safety (treated as of April 7, 2022 with ≥1 Q6W tumor-imaging assessment). Patients had immunologically cold and/or immunotherapy resistant tumors and were heavily pretreated: 61% received ≥3 prior lines of therapy including 34% prior immunotherapy. Median follow-up was 6.1 months.

Disease-specific combination therapy cohorts are being expanded with BOT at 1 or 2mg/kg or 150mg+BAL (including 4 crossover patients): (1) microsatellite stable (MSS) colorectal cancer (n=44, ORR 25%), (2) platinum resistant ovarian cancer (n=18, ORR 28%), (3) sarcoma (n=12, ORR 42%, and (4) PD-(L)1 relapsed/refractory non-small cell lung cancer (n=3, ORR 67%).

The ORR was 22% (22/98; 3 CR/19 PR) with median duration of response [DOR] not reached (range,1.4+ to 19.5+ months) in all combination patients (BAL+BOT 0.1-2 mg/kg or 150 mg); 13/22 responses are ongoing. In addition, 15% (2/13) monotherapy patients achieved PR after crossing over to combination therapy. The ORR was 11% (5/44; 1 CR/4 PR) in all monotherapy patients (BOT 0.1-3 mg/kg). Responses were independent of PD-L1 expression and tumor mutation burden. Further evaluation of biomarkers is ongoing including paired biopsies (before/during treatment).

Grade 1/2, 3 or 4 treatment-related adverse events (TRAE) occurred in 88%, 29%, 2% respectively. Diarrhea/colitis (19%) was the only grade 3/4 TRAE occurring in ≥5% of patients. There were no cases of hypophysitis or myocarditis. Pneumonitis occurred in 4 patients (3%). Two patients had grade 5 TRAEs (enterocolitis, colonic perforation).

Conclusions BOT±BAL demonstrates remarkable activity in heavily pretreated patients with solid tumors historically unresponsive to immunotherapy. The safety profile is consistent with the mechanism of action of BOT. Randomized studies in MSS CRC, pancreatic cancer, and melanoma are planned to open this year.

Trial Registration NCT03860272

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