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640 The combination of COM701 + nivolumab demonstrates preliminary antitumor activity in patients with metastatic breast cancer
  1. Ecaterina Dumbrava1,
  2. Bartosz Chmielowski2,
  3. Dale Shepard3,
  4. Daniel Vaena4,
  5. Drew Rasco5,
  6. Manish Sharma6,
  7. Erika Hamilton7,
  8. Kyriakos P Papadopoulos8,
  9. Judy S Wang9,
  10. Eran Ophir10,
  11. Pierre Ferre11,
  12. Inbal Barbiro10,
  13. Gady Cojocaru10,
  14. Adeboye H Adewoye12 and
  15. Manish Patel13
  1. 1The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  2. 2University of California Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA
  3. 3Cleveland Clinic Cancer Center, Cleveland, OH, USA
  4. 4West Cancer Center and Research Institute, Germantown, TN, USA
  5. 5START, San Antonio, TX, USA
  6. 6START Midwest, Chicago, IL, USA
  7. 7Sarah Cannon Research Institute, Nashville, TN, USA
  8. 8START San Antonio, San Antonio, TX, USA
  9. 9Florida Cancer Specialists/SCRI, Sarasota, FL, USA
  10. 10Compugen Ltd., Holon, Israel
  11. 11Compugen, Toulouse, France
  12. 12Compugen USA Inc., San Francisco, CA, USA
  13. 13Florida Cancer Specialists, Sarasota, FL, USA
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background COM701, a novel, first in-class immune checkpoint inhibitor, anti-PVRIG, that leads to activation of T-cells. PVRL2, the ligand of PVRIG, is highly expressed in breast cancer. We have reported preliminary antitumor activity with objective responses [partial responses and a complete response] in patients with solid tumors (MSS-CRC, platinum resistant OVCA, anal squamous CA, MSS-endometrial cancer] who received COM701 +/- nivolumab + BMS-986207 (anti-TIGIT antibody).1 2 We present results from the dose expansion cohort with COM701 + nivolumab in patients with metastatic breast cancer (MBC) (NCT03667716).

Methods We enrolled 17 patients with MBC, all received COM701 20 mg/kg + nivolumab 480 mg, both IV Q4 weeks. Primary objectives were to determine safety and tolerability and secondary objective was to evaluate preliminary antitumor activity. Key inclusion criteria: Age ≥ 18 years, histologically confirmed locally advanced or MBC (regardless of ER/PR and HER2 status) with measurable disease, who exhausted all available standard treatments. Prior treatment with anti-PD-(L)-1, anti-CTLA-4 ICI was permissible. Key exclusion criteria: history of immune-related events that to immunotherapy treatment discontinuation, history of pneumonitis. Safety was evaluated per CTCAE v4.03 and investigator responses per RECIST v1.1.

Results Treatment related adverse events reported in 12/17 (71%) patients, the majority [11/12 pts] were ≤G2, the most frequent was diarrhoea in 3 pts (all G1). One patient with G3 TRAE of pneumonitis (recovered), no ≥G4 TRAEs. Tumor assessments (by site): PD-L1 negative 9/17 (53%), positive/present 2/17 (12%), missing/not assessed 6/17 (35%); TMB low (<10 mut/MB) in 10/17 (59%), missing/not assessed 7/17 (41%). Objective response rate 2/17 patients (12%) - a CR was achieved in a patient with ER+/PR-, HER2- invasive ductal carcinoma (pretreatment: PD-L1 CPS 3, PVRL2 tumor H-score 300 (both by sponsor assessment), TMB-low (5 Mut/Mb)] who received 3 prior lines of therapy and continues the study treatment (567 days). Another patient with TNBC, PD-L1 negative, TMB-low (1 Mut/Mb), with 4 prior lines of therapy with a PR remained on study treatment (296 days), 3 pts with stable disease, all PDL1 CPS<1 and low TMB. Disease control rate [CR+PR+SD] 5/17 (29%). Patients with clinical benefit and serum samples available showed increased IFNg at Cycle 2–3 compared to baseline.

Conclusions The combination is well tolerated with no dose-limiting toxicity. Encouraging preliminary antitumor activity with PR and CR reported in heavily pretreated patients with TMB-low MBC. Additional clinical and translational data will be presented at the conference. Data extract 06/09/2023.

Acknowledgements We thank the patients for participating in this clinical trial and their families, the investigators and their staff at the clinical trial sites; Study Sponsor Compugen Ltd in collaboration with Bristol Myers Squibb; Danae Hudson, Amanda Harp, Compugen USA Inc for clinical operations oversight of the study

Trial Registration NCT03667716.

References 1. Moroney JA, Yeku O et al. Triple blockade of the DNAM-axis with COM701 + BMS-986207 + nivolumab demonstrates preliminary antitumor activity in patients with platinum resistant OVCA. Annals of Oncology (2022);16 (suppl_1): 100104–100104. 10.1016/iotech/iotech100104

2. Drew Rasco, Ecaterina Dumbrava et al. COM701 plus nivolumab demonstrates preliminary antitumor activity and immune modulation of tumor microenvironment in patients with metastatic MSS-CRC and liver metastases. Journal for Immunotherapy of Cancer Nov 2022;10 (Suppl 2) A690; DOI: 10.1136/jitc-2022-SITC2022.0659

Ethics Approval The study obtained ethics approval from the IRBs below:

1. IntegReview SSU00166554

2. Salus IRB IRB00013027

3. WIRB 20181858

4. IRB at Cleveland Clinic IRB#19–238

5. IRB University of Chicago IRB18–0806

6. OHRS at Dana Farber Institute 18–555

7. Columbia University IRB IRB-AAAR9998

8. UCLA OHRPP IRB#18–001383

9. IRB of MD Anderson 2018–0891

10. Salus IRB IRB00013027

11. Advarra Pro00052320

All participants gave informed consent before taking part.

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