MyTACTIC: Afficacy and safety of atezolizumab (atezo) + chemotherapy (chemo) in patients (pts) with advanced unresectable/metastatic solid tumors with high tumor mutational burden (TMB-H) or high microsatellite instability (MSI-H)/deficient mismatch repair (dMMR).

Abstract

2612 Background: MyTACTIC (NCT04632992) is a phase II, non-randomized, multi-arm basket study evaluating targeted therapies as single agents or combinations in pts with advanced solid tumors with specific biomarkers. We present the efficacy and safety of arm E from MyTACTIC: atezo + chemo in pts whose tumors have TMB-H and/or MSI-H/dMMR. Methods: Enrolled pts were ≥18 years old, with histologically/cytologically confirmed advanced unresectable/metastatic solid tumors with TMB-H (TMB≥10 mut/Mb) and/or MSI-H/dMMR and ECOG PS ≤2; those with symptomatic/actively progressing CNS metastases were excluded. Pts received intravenous atezo 1200 mg every 21 days and physician’s choice chemo (docetaxel; paclitaxel; capecitabine) until progressive disease (PD), toxicity or death. Primary endpoint: investigator-assessed confirmed objective response rate (cORR). Secondary endpoints included disease control rate (DCR; confirmed complete response [CR] + partial response [PR] + stable disease [SD] or non-CR/non-PD for ≥70 days), duration of response (DOR), progression-free survival (PFS) and safety. Results: At data cutoff (May 16, 2022), 25 pts with 10 tumor types had received atezo + chemo. Median age was 69 years (range 37–83), 88% of pts had ECOG PS ≤1 and 20 pts with metastatic disease had a median of 1 prior line of therapy (range 1–4). Twenty-three pts had TMB-H (2 missing), 7 had MSI-H and 7 had dMMR (12 missing); 7 pts had TMB-H and MSI-H/dMMR. cORR was 28.0% (7/25; 95% CI 12.1–49.4), including 1 CR (colon cancer) and 6 PRs. Responses were observed in 6/10 tumor types studied. cORR was 12.5% in pts with TMB-H alone (2/16) and 71.4% (5/7) in pts with TMB-H and MSI-H/dMMR. DCR was 32.0% (8/25; 95% CI 14.9–53.5). Median DOR and median PFS were 7.4 months (95% CI 7.4–not estimable) and 3.9 months (95% CI 2.2–8.4), respectively. The safety profile of atezo + chemo was consistent with previous reports for this combination. The most common treatment-related adverse events (TRAEs) were diarrhea (60%) and fatigue (32%). Grade 3/4 TRAEs occurred in 32% of pts and there were no serious or grade 5 TRAEs. Conclusions: In this small cohort, treatment with atezo + chemo demonstrated clinical activity in pts with advanced solid tumors with TMB-H and/or MSI-H/dMMR. Responses were observed in different tumor types and were numerically higher in pts whose tumors had both biomarkers vs those with TMB-H alone. Further analyses with a larger cohort and longer follow-up will be required to confirm these results. Clinical trial information: NCT04632992 . [Table: see text]