COM701 with or without nivolumab: Results of an ongoing phase 1 study of safety, tolerability and preliminary antitumor activity in patients with advanced solid malignancies (NCT03667716).
Authors: Vaena Daniel A. , Fleming Gini F. , Chmielowski Bartosz , Sharma Manish , Hamilton Erika P. , Sullivan Ryan J. , Shepard Dale Randall , Papadopoulos Kyriakos P. , Patnaik Amita , ElNaggar Adam , Adewoye Adeboye H. , Smith Robina , Lim Emerson A. , Dumbrava Ecaterina Elena , Rasco Drew W. 
Published: June 2021

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Background: COM701 is a novel first in class humanized IgG4 monoclonal antibody that binds with high affinity to poliovirus receptor related immunoglobulin domain containing (PVRIG), blocking its interaction with its ligand, PVRL2. Blocking of PVRIG leads to enhanced activation of T/NK cells and in mouse models inhibits tumor growth. We report new and updated results on safety/tolerability/pharmacokinetics and antitumor activity from this ongoing study including final results in dose escalation combination cohort, monotherapy expansion cohort (MEC). Methods: We enrolled a total of 51 DLT-evaluable pts: Arm A (COM701 mono dose escalation), 16 pts in 8 cohorts (0.01 – 20 mg/kg IV Q3/4 wks); Arm B (COM701 0.3 – 20 mg/kg + nivolumab (NIVO) 360 mg/480 mg IV Q3/Q4 wks), 15 pts in 5 cohorts; 20 pts in MEC (NSCLC, OVCA, breast, endometrial and CRC) at the recommended dose for expansion(RDFE), 20 mg/kg IV Q4 wks. Key inclusion criteria: Age ≥18 yrs, histologically confirmed metastatic solid malignancy, has exhausted available standard tx, ECOG 0-1, prior ICI permissible (except prior tx with a PVRIG inhibitor). Key exclusion criteria: active autoimmune disease requiring systemic tx, hx inflammatory lung disease. Primary objectives – safety/tolerability of COM701 ± NIVO (AEs, CTCAE v4.03), PK, RDFE. Key secondary/exploratory objectives - antitumor activity of COM701 ± NIVO (RECIST v1.1), evaluation of PVRL2 expression in tumor biopsy, blood cytokines and immunophenotyping. Results: No DLTs were reported in Arms A or B. COM701 PK profile similar in Arm A, 20 mg/kg IV Q4 wks (cohort 8) and Arm B cohort 5 (COM701 20 mg/kg + NIVO 480 mg; all IV Q4 wks). Frequency of TEAEs in safety population (N=54 pts): pts on COM701 mono (N=38)- No AE (4), Grade≤2 (21), G3 (11), G4 (1), G5 (1, PD), pts on combo (N=16) - Grade≤2 (8), G3 (7), G5 (1, PD). Serious TEAE: pts on COM701 mono 11/38, pts on combo 6/16. Most frequent AEs in Arm A: Grade ≤2 fatigue 12/38 pts (31%), nausea 9/38 (23%); Arm B: fatigue 7/16 pts (44%) and AST increased 4/16 pts (25%). Antitumor activity - in Arm A (cohort 8), a pt with platinum resistant primary peritoneal cancer had confirmed PR ongoing 14 months. In Arm B (COM701 10 mg/kg + NIVO 480 mg, all IV Q4 wks), a pt with anal SCCA; confirmed CR, ongoing 18 months, last tx with prior PD on NIVO. In addition, a pt with renal cell CA had confirmed SD [ongoing 13 months, COM701 0.3 mg/kg + NIVO 360mg; IV Q3 wks],] In MEC, 30% (6/20 pts) had best response of SD [1-endometrial, 3 NSCLC, 2 OVCA], 2 pts [NSCLC, OVCA] ongoing at 6/4 months. Overall 16pts had prior tx-refractory disease, 9(56%) had best response of ≥SD. Of 18 pts with prior tx with ICI, 13 (72%) had best response of ≥SD. Datacut 14Dec2020. Conclusions: COM701 ± NIVO well tolerated with no new safety signals. Encouraging signal of antitumor activity including in pts with prior tx with ICI or prior tx-refractory disease. Clinical trial information: NCT03667716..