198P - Inavolisib in cancers with activating PIK3CA mutations: Results from the CRAFT trial

Background

CRAFT (Continuous ReAssessment with Flexible ExTension in Rare Malignancies) is an open-label, 7-arm, cross-entity phase 2 trial investigating the efficacy of combinations of molecularly targeted agents and PD-L1 inhibition with atezolizumab in cancers with targetable molecular alterations (PMID: 34808524). We report the interim efficacy analysis of inavolisib in cancers with activating PIK3CA mutations.

Methods

Adult patients with locally advanced/metastatic cancer refractory to ≥1 medical treatment and selected molecular tumor characteristics (arm 1: BRAF V600E/K mutations; arm 2: ERBB2 amplification/overexpression, activating ERBB2 mutations; arm 3: ALK rearrangements/ALK mutations; arm 4: aberrations predicting increased PI3K-AKT pathway activity; arm 5: activating PIK3CA mutations; arm 6: aberrations predicting increased RAF-MEK-ERK pathway activity; arm 7: alterations predicting anti-PD-L1/anti PD-1 sensitivity) were eligible. Main exclusion criteria were hematologic/primary brain cancers. In arm 5, inavolisib 9 mg q.d. was given. Statistics are based for each arm on a Simon’s optimal 2-stage design with 14 patients accrued in stage I. If ≥4 patients achieve disease control (complete/partial remission [CR/PR] or stable disease [SD] according RECIST 1.1) at day 110, an additional 11 patients will be accrued in stage II.

Results

As of 04/2024, 91 patients were registered, and 63 were treated within CRAFT, including 25 patients with PIK3CA-mutated tumors in arm 5. Assessment of the primary endpoint in arm 5 in the 14 patients accrued in stage I showed a disease control rate at day 110 of 36 % (5 of 14 patients), including 2 PRs (urothelial cancer, thyroid cancer), thus leading to the accrual of an additional 11 patients in stage II until 03/2024. Main toxicity was hyperglycemia. Currently, 10 patients showed disease control at interim tumor assessment at week 8, while 7 are still on treatment with tumor assessment pending.

Conclusions

In this first analysis, inavolisib showed promising disease control rates in a cross-entity patient population including rare tumors. Final results for the full cohort, including results from in-depth molecular tumor analyses will be presented at the meeting.

Clinical trial identification

NCT04551521; EudraCT 2019-003192-18.

Editorial acknowledgement

Legal entity responsible for the study

German Cancer Research Center, Heidelberg, Germany.

Funding

This trial is supported by the NCT Proof-of-Concept Clinical Trial Program and the NCT Molecular Precision Oncology Program. Study drugs are provided free of charge by Roche Pharma AG.

Disclosure

C.E. Heilig: Financial Interests, Institutional, Research Funding: AstraZeneca, Pfizer, PharmaMar, Roche. A. Desuki: Financial Interests, Personal, Advisory Board: BMS, MSD, Roche; Financial Interests, Personal, Invited Speaker: Janssen-Cilag. B. Deschler: Financial Interests, Personal, Expert Testimony: Eli Lilly; Financial Interests, Personal, Other, Travel Expenses: Eli Lilly. V. Kunzmann: Financial Interests, Personal, Advisory Board, Advisory Role: Amgen, BMS, AstraZeneca, Pierre Fabre Pharma, MSD; Financial Interests, Institutional, Coordinating PI: AstraZeneca, BMS; Non-Financial Interests, Principal Investigator: AstraZeneca, BMS. N. von Bubnoff: Financial Interests, Personal, Other, Honoraria: Janssen, BMS; Financial Interests, Personal, Other, Honoraria Honoraria: Novartis; Financial Interests, Personal, Other, Travel Expenses: Janssen. L. Illert: Financial Interests, Personal, Advisory Board: AbbVie, Janssen-Cilag, Roche; Financial Interests, Personal, Other, Honoraria: Roche, AstraZeneca, Ars Tempi, Takeda, Illumina; Financial Interests, Personal, Other, Travel/accommodation expenses: Roche, AstraZeneca, Janssen-Cilag, Takeda. D.T. Rieke: Financial Interests, Personal, Advisory Board: Bayer, Alacris Theranostics; Financial Interests, Personal, Invited Speaker: Roche, BMS, Lilly; Non-Financial Interests, Principal Investigator: Bayer. P. Horak: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Platomics. S. Fröhling: Financial Interests, Personal, Advisory Board: Bayer, Illumina, Roche; Financial Interests, Personal, Invited Speaker: Amgen, Eli Lilly, Illumina, PharmaMar, Roche. R.F. Schlenk: Financial Interests, Institutional, Research Funding: AstraZeneca, Boehringer Ingelheim, Pfizer, PharmaMar, Roche, Daiichi Sankyo, Recordati; Financial Interests, Personal, Speaker’s Bureau: Daiichi Sankyo, Pfizer, AbbVie, Astellas; Financial Interests, Personal, Advisory Board: AbbVie, Daiichi Sankyo, Jazz, Pfizer. All other authors have declared no conflicts of interest.