On December 19, 2022, Arcus Biosciences, Inc. (the "Company") reported positive results from the fourth interim analysis of ARC-7, its randomized, 150-patient Phase 2 trial in first-line metastatic PD-L1≥50% non-small cell lung cancer in which the Company is studying domvanalimab in combination with zimberelimab both with and without etrumadenant vs. zimberelimab monotherapy (Press release, Arcus Biosciences, DEC 19, 2022, View Source [SID1234625393]). This interim analysis was conducted at the clinical data cutoff date of August 31, 2022.
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At the time of data cutoff, efficacy was evaluated in patients who had at least 13 weeks of follow-up and were therefore potentially eligible for at least two imaging scans (n=133), and safety was evaluated in all enrolled patients (n=149). With a median follow-up time for efficacy duration of approximately 12 months, both the doublet and triplet combinations demonstrated clinically meaningful improvements in median progression-free survival (PFS) and six-month landmark PFS rates compared to zimberelimab monotherapy, with a 45% reduction in risk of disease progression or death for the doublet and 35% for the triplet.
Each of the domvanalimab-containing study arms also demonstrated clinically meaningful improvements in objective response rate (ORR) compared to zimberelimab monotherapy. Confirmed ORR was 27%, 41% and 40% for the zimberelimab monotherapy arm and the domvanalimab-doublet and -triplet arms, respectively. While the triplet arm did not show an improvement over the doublet arm, it reinforces the results observed in the doublet arm, and the study will continue to monitor PFS, as well as overall survival, for the triplet arm as these data mature.
The efficacy results including ORR and PFS are summarized in the table below:
Endpoint
zimberelimab (Z) monotherapy
(n=44)
domvanalimab + zimberelimab (DZ)
(n=44)
etrumadenant + domvanalimab +
zimberelimab (EDZ) (n=45)
Progression-free Survival (PFS)
Median in Months (95% CI)
5.4 (1.8, 9.6)
12.0 (5.5, NE)
10.9 (4.8, NE)
Hazard Ratio* (95% CI)
0.55 (0.31, 1.0)
0.65 (0.37, 1.1)
Six-month PFS rate (95% CI)
43% (27, 59)
65% (49, 80)
63% (48, 78)
Objective Response Rate (ORR)
ORR+ (95% CI)
27% (15.0, 42.8)
41% (26.3, 56.8)
40% (25.7, 55.7)
*Hazard ratio is for comparing domvanalimab-containing study arms to zimberelimab monotherapy.
+Based on confirmed response per RECIST 1.1
NE=not evaluable
No unexpected safety signals were observed across the three study arms at the time of data cutoff. The domvanalimab-containing study arms appeared to be generally well tolerated and showed an overall safety profile consistent with the known safety profiles of each individual molecule to date. Grade ≥3 treatment-emergent adverse events occurred in 58% of participants in the zimberelimab monotherapy study arm, 47% of the doublet arm, and 52% of the triplet arm. Incidence of infusion-related reactions was low across all treatment arms: 4%, 4% and 10% for zimberelimab monotherapy and the domvanalimab-doublet and -triplet arms, respectively. Immune-related adverse events, including the incidences and grades of rash and pruritus, were generally low and manageable with topical corticosteroids.