181O - Interim analysis (IA) of the atezolizumab (atezo) + sacituzumab govitecan (SG) arm in patients (pts) with triple-negative breast cancer (TNBC) in MORPHEUS-pan BC: A phase Ib/II study of multiple treatment (tx) combinations in pts with locally advanced/metastatic BC (LA/mBC)

Background

Cancer immunotherapy has transformed the TNBC tx landscape but new combinations are needed to further improve survival outcomes. Atezo (PD-L1 inhibitor) + nab-paclitaxel (nab-P) is approved for first-line (1L) tx of PD-L1+, inoperable LA/mTNBC. SG (Trop-2-directed antibody–drug conjugate) is approved for 2L+ tx of mTNBC. We present the 18-week IA of the atezo + SG arm in MORPHEUS-panBC (NCT03424005).

Methods

Eligible pts with no prior systemic tx for PD-L1+, inoperable LA/mTNBC were randomised to receive control (atezo 840 mg IV on Day [D] 1 & 15 + nab-P 100 mg/m² IV on D1, 8 & 15, of 28-D cycles) or atezo (1200 mg IV, D1) + SG (10 mg/kg IV, D1 & 8) of 21-D cycles, until unacceptable toxicity/loss of clinical benefit. Primary endpoints were objective response rate (ORR) and safety. Baseline tumours were evaluated for TROP-2 and PD-L1 IC expression for associations with response.

Results

At data cut-off (9 March 2023) 11 pts were enrolled in the control arm and 31 in the atezo + SG arm. More pts were aged <65 years in the atezo + SG arm (84%) vs. control (64%); liver and brain metastatic site distribution was similar between arms. ORR was 76.7% (n = 23; 5 complete responses) with atezo + SG vs. 66.7% (n = 6; all partial responses) with control; clinical benefit rate (CBR) was 83.3% vs. 66.7% (see table). Median (m) progression-free survival (PFS) data were immature but showed a trend towards benefit with atezo + SG vs. control (12.2 vs. 5.9 months [mo]; median follow-up: 10.6 vs. 11.7 mo). No new safety signals were seen; overall safety summary is shown in the table. Table: 181O

* Efficacy- and safety-evaluable pts.

Conclusions

Encouraging activity was seen with 1L atezo + SG tx in pts with PD-L1+ LA/mTNBC. PFS data were immature but showed a trend towards benefit with atezo + SG. Safety of atezo + SG was consistent with the profiles of the individual drugs, with no new safety signals seen.

Clinical trial identification

NCT03424005; 05/02/2018.

Editorial acknowledgement

Support for third-party writing assistance for this abstract, furnished by Brian Law, PhD, of Nucleus Global, an Inizio company.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

P. Schmid: Financial Interests, Personal, Other, Honoraria: Pfizer, AstraZeneca, Novartis, Gilead, F. Hoffmann-La Roche Ltd., Merck, MSD, BI, Seagen, Amgen, Bayer, Eisai, Celgene, Lilly, Puma; Financial Interests, Personal, Advisory Role: Pfizer, AstraZeneca, Novartis, Gilead, F. Hoffmann-La Roche Ltd., Merck, MSD, BI, Seagen, Amgen, Bayer, Eisai, Celgene, Lilly, Puma; Financial Interests, Institutional, Research Grant: AstraZeneca, Genentech, Inc., F. Hoffmann-La Roche Ltd., Oncogenex, Novartis, Astellas, Medivation; Non-Financial Interests, Personal, Other, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd. S. Loi: Financial Interests, Institutional, Expert Testimony: Aduro Biotech, Amunix, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, G1 Therapeutics, Gilead Therapeutics, GSK, Merck, Novartis, Pfizer, Puma Biotechnology, F. Hoffmann-La Roche Ltd/Genentech, Inc., Seattle Genetics, Silverback Therapeutics, Tallac Therapeutics; Financial Interests, Institutional, Advisory Board: Aduro Biotech, Amunix, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, G1 Therapeutics, Gilead Therapeutics, GSK, Merck, Novartis, Pfizer, Puma Biotechnology, F. Hoffmann-La Roche Ltd/Genentech, Inc., Seattle Genetics, Silverback Therapeutics, Tallac Therapeutics; Financial Interests, Institutional, Other, Consultancy: Aduro Biotech, Amunix, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, G1 Therapeutics, Gilead Therapeutics, GSK, Merck, Novartis, Pfizer, Puma Biotechnology, F. Hoffmann-La Roche Ltd/Genentech, Inc., Seattle Genetics, Silverback Therapeutics; Financial Interests, Institutional, Officer, Consultancy: Tallac Therapeutics; Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, Eli Lilly, Merck, Nektar Therapeutics, Novartis, Puma Biotechnology, F. Hoffmann-La Roche Ltd/Genentech, Inc., Seattle Genetics; Non-Financial Interests, Personal, Advisory Role: AstraZeneca, Bristol Myers Squibb, Eil Lilly, Gilead Therapeutics, Merck, Novartis, Pfizer, F. Hoffmann-La Roche Ltd/Genentech, Inc., Seattle Genetics; Non-Financial Interests, Personal, Other, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd. L. De la Cruz Merino: Financial Interests, Personal, Advisory Role: BMS, MSD-Merck, Pierre-Fabre, Gilead, Daiichi Sankyo, Immunocore, Incyte; Non-Financial Interests, Personal, Other, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd. R. Yerushalmi: Financial Interests, Personal, Advisory Role: Pfizer, AstraZeneca, Novartis, Gilead, F. Hoffmann-La Roche Ltd., MSD, Lilly, Rhenium Medison, Stemline; Financial Interests, Personal, Other, Honoraria: Pfizer, AstraZeneca, Novartis, Gilead, F. Hoffmann-La Roche Ltd., MSD, Lilly, Rhenium Medison, Stemline; Financial Interests, Personal, Research Grant: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Other, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd. S. Im: Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Daiichi Sankyo, Eisai, GSK, Hanmi, Lilly, MSD, Novartis, Pfizer, F. Hoffmann-La Roche Ltd/Genentech, Inc; Financial Interests, Institutional, Research Grant: AstraZeneca, Boryung Pharmaceutical, Daewoong Pharmaceutical, Eisai, Pfizer, F. Hoffmann-La Roche Ltd/Genentech, Inc; Non-Financial Interests, Personal, Other, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd. A. Sonnenblick: Financial Interests, Personal, Advisory Role: AstraZeneca, Eli Lilly, F. Hoffman-La Roche Ltd., Gilead, MSD, Novartis, Pfizer, Progenetics; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly, F. Hoffmann-La Roche Ltd., Novartis, Teva; Financial Interests, Institutional, Research Grant: F. Hoffmann-La Roche Ltd., Novartis; Financial Interests, Personal, Other, Travel, accommodation expenses: Celgene, F. Hoffmann-La Roche Ltd., Medison, MSD, Neopharm; Non-Financial Interests, Personal, Other, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd. M. Martinez Garcia: Financial Interests, Personal, Advisory Role: Lilly, Novocure, Saegen, Boehringer Ingelheim, Pierre Fabre; Financial Interests, Personal, Speaker’s Bureau: Novocure; Financial Interests, Personal, Other, Honoraria: Lilly, AstraZeneca; Financial Interests, Personal, Other, Travel, accommodations, expenses: Pfizer, Gilead, AstraZeneca, Daiichi Sankyo; Non-Financial Interests, Personal, Other, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd. I. Moreno Candilejo: Financial Interests, Personal, Advisory Role: Ellipses Pharma; Non-Financial Interests, Personal, Other, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd. L.C. Kennedy: Non-Financial Interests, Personal, Other, Consultant: Daiichi Sankyo; Non-Financial Interests, Personal, Research Grant: Puma Biotechnology; Non-Financial Interests, Personal, Other, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffman-La Roche Ltd. K.L. Griffiths: Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Full or part-time Employment: Genentech, Inc; Non-Financial Interests, Personal, Other, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffman-La Roche Ltd. R. Schwab: Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Full or part-time Employment: Genentech, Inc; Non-Financial Interests, Personal, Other, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffman-La Roche Ltd. F. Young: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Other, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd. L. Liao: Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Full or part-time Employment: Genentech, Inc; Non-Financial Interests, Personal, Other, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffman-La Roche Ltd. K. Dupree: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.; Non-Financial Interests, Personal, Other, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd. S. Kim: Financial Interests, Institutional, Principal Investigator: Novartis, Sanofi-Aventis, DongKook Pharm Co.; Financial Interests, Personal, Advisory Role: Novartis, AstraZeneca, Lilly, Dae Hwa Pharmaceutical Co. Ltd., ISU Abxis, OBI Pharma, BeiGene, Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares: Genopeaks.