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).

David R. Spigel Department of Thoracic Medical Oncology, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN info_outline David R. Spigel, Maen A. Hussein, Richard Zuniga, Daruka Mahadevan, Robert Winn, Walter C. Darbonne, Bongin Yoo, Young Kim, Zach Whitehead, Ari M. Vanderwalde

Authors David R. Spigel Department of Thoracic Medical Oncology, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN info_outline David R. Spigel, Maen A. Hussein, Richard Zuniga, Daruka Mahadevan, Robert Winn, Walter C. Darbonne, Bongin Yoo, Young Kim, Zach Whitehead, Ari M. Vanderwalde Organizations Department of Thoracic Medical Oncology, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN, Florida Cancer Specialists – Sarah Cannon Research Institute, Leesburg, FL, Precision Medicine, OneOncology, Inc., Nashville, TN and New York Cancer and Blood Specialists, Port Jefferson Station, NY, Division of Hematology and Medical Oncology, Mays Cancer Center, University of Texas Health San Antonio MD Anderson Cancer Center, San Antonio, TX, Department of Health Behavior and Policy, Virginia Commonwealth University, Richmond, VA, US Medical Affairs Oncology, Genentech, Inc., South San Francisco, CA, West Cancer Center and Research Institute, Caris Life Sciences, Germantown and Memphis, TN Abstract Disclosures Research Funding Pharmaceutical/Biotech Company This study is sponsored by Genentech, Inc. Third-party medical writing assistance, under the direction of authors, was provided by Vanessa Poon, BSc, of Ashfield MedComms, an Inizio company, and was funded by Genentech, Inc 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. Tumor type cORR n/N Colon 2/11; 18% Breast 1/5; 20% Bladder 1/1 NSCLC 1/1 Uterine 1/1 Carcinoma of unknown primary 1/1 Esophageal (n=2)*, Neuroendocrine (n=1), Prostate (advanced unresectable n=1), Prostate (metastatic n=1) 0/5 *DCR: 50%; 1 pt had SD for ≥70 days.

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