Activity and safety of ipatasertib (ipat) for AKT activating mutation and/ or PTEN loss/loss of function solid tumors from MyTACTIC

Background: MyTACTIC (NCT04632992) is a multiarm basket study evaluating the safety/efficacy of targeted therapies as single agents or combinations in advanced unresectable/metastatic solid tumors with specific genomic alterations. We analyzed potent oral AKT inhibitor ipat pan-tumor population activating mutation and/or PTEN loss/loss function from MyTACTIC. Materials and Methods: Enrolled patients (pts) were ≥18 years old had AKT1/2/3 and/ alteration. Pts received 400 mg/day. The primary endpoint was investigator-assessed confirmed objective response rate (cORR; complete [CR]+partial [PR]). Other key endpoints: disease control (DCR; CR+PR+stable non-CR/ non-progressive [PD] ≥98 days [28-day arms] ≥70 [21-day arms]); progression-free survival (PFS); duration (DOR); safety. Results: At data cutoff (Jan 24, 2022), 26 pts various tumor types (AKT mutations, n = 5; PTEN, 21). median 3 (range 1–8) prior lines therapy for metastatic disease. cORR 11.5% (n 3/26); DCR 34.6% 9/26). Median DOR not reached (95% CI 3.7–not estimable); PFS 3.6 mos 1.9– 7.1). Best overall per type AKT/PTEN status presented Table. Adverse events (AEs) consistent known safety profile ipat. most common treatment-related AEs (TRAEs) diarrhea (65.4%) nausea (30.8%). Grade seen 7/26 (26.9%) 4 1/26 (3.8%; perirectal abscess) pt; no 5 AE seen. 2/26 (7.7%) serious TRAEs: 1 pt discontinued treatment due to TRAEs.Table(abstract: 198 (PB078))Cancer TypeTotal ptsPR, (mutation*High-level biomarker listed PRs only here. Protocol-allowed biomarkers included mutations loss via IHC mutation., lines)SD†6 SD >4 months., (prior lines)PD, lines)Non-CR/non-PD, lines)Non Evaluable, nMissing, nBreast71 (AKT1:E17 K, 5+)4 2–5+)1 (3)1Prostate74 (~3–4)2 (4; 5+)1Colon31 (4)2 (3; 4)Colorectal21 (PTEN loss, 3)1 (2)Endometrial21 2)1Rectal11 (1)Anal21 (3)1 (5+)Cervical11 (2)Adenocarcinoma (Neck)11Grand Total, n263810113* High-level mutation.† 6 months. Open table new tab Conclusions: In this small cohort, single-agent showed some clinical activity heavily pretreated heterogeneous cancers. Further investigation role inhibition (AKTi) potential resistance mechanisms warranted. Given rationale AKTi+endocrine (ET) HR+ HER2– mBC, ipat+ET being evaluated Phase FINER (NCT04650581) 2 FAIM (NCT04920708) trials. Conflict interest: Ownership: W.C.D an employee shareholder Roche/Genentech, Inc. W.Y owns stocks Roche. Y.K T.S Advisory Board: A.VW has advisory board fees Bristol Myers Squibb, Mirati, consulting George Clinical, Elsevier. Substantive Relationships: Caris Life Sciences. Z.W Rutgers University contracted by Genentech, D.R.S reports paid institution Amgen, AZ, BeiGene, BMS, Curio Science, EMD Serono, Evidera, Exelixis, Genentech/Roche, GlaxoSmithKline, Intellisphere, Janssen, Jazz Pharmaceuticals, Lilly, Mirati Therapeutics, Molecular Templates, Novartis, Novocure, Pfizer, Puma Biotechnology, Regeneron, Sanofi-Aventis research grants Aeglea Biotherapeutics, Agios, Apollomics, Arcus, Arrys Astellas, Bayer, BIND BioNTech RNA Blueprint Medicine, Boehringer-Ingelheim, Bristol-Myers Calithera, Celgene, Celldex, Clovis, Cyteir Daiichi Sankyo, Denovo Biopharma, Eisai, Elevation Oncology, Evelo Biosciences, G1 GSK, GRAIL, Hutchison MediPharma, ImClone Systems, Incyte, ImmunoGen, Ipsen, Kronos Bio, Loxo MacroGenics, MedImmune, Merck. Partners, Template, Nektar, Neon Oncologie, PTC PureTech Health, Razor Genomics, Repare Rgenix, Takeda, Tesaro, Tizona Transgene, UT Southwestern, Verastem. E.A, D.S R.Z have conflicts disclose.