13P - Brain metastases and actionable genetic alterations with sacituzumab govitecan versus docetaxel in metastatic non-small cell lung cancer: Subgroups of the phase III EVOKE-01 trial

Background

EVOKE-01 (NCT05089734) is a phase III study assessing patients with metastatic non-small cell lung cancer (mNSCLC) who progressed after platinum-based chemotherapy and anti–programmed death (ligand)-1 (PD-[L]1) treatment. The primary endpoint of overall survival (OS) was not statistically significant. Numerical improvement in OS was observed with sacituzumab govitecan (SG) compared with docetaxel (hazard ratio [HR], 0.84; 95% CI, 0.68–1.04). We report EVOKE-01 efficacy in subgroups with brain metastases and actionable genetic alterations (AGAs).

Methods

Patients were randomized 1:1 to receive SG (10 mg/kg IV; days 1, 8) or docetaxel (75 mg/m² IV; day 1) in 21-day cycles. Key secondary endpoints included investigator-assessed progression-free survival (PFS) and objective response rate (ORR). Descriptive statistics are reported for subgroups in this post-hoc analysis.

Results

Of the 603 patients randomized in EVOKE-01 (299 SG, 304 docetaxel), 74 (12.3%) had known brain metastases at baseline (35 [11.7%] SG, 39 [12.8%] docetaxel) and 44 (7.3%) had a known AGA (19 [6.4%] SG, 25 [8.2%] docetaxel). EGFR (n=19), KRAS (n=14), and MET (n=5) were the most common AGAs. Median (range) age was 59 (31–79) years for patients with brain metastases and 63 (40–79) years for patients with AGAs; 51 (68.9%) and 20 (45.5%) patients were male, respectively. Median (95% CI) OS for patients with brain metastases was 12.1 (6.8–not reached [NR]) months with SG and 7.3 (5.6–10.6) months with docetaxel (HR, 0.62; 95% CI, 0.34–1.13). Median (95% CI) OS for patients with AGAs was NR (7.2–NR) months with SG and 7.0 (5.2–11.6) months with docetaxel (HR, 0.52; 95% CI, 0.22–1.23). See table for PFS and ORR.

Subgroup of patients with brain metastases or a known AGA at baseline, summary of efficacy

^a2-sided CI based on Clopper-Pearson method Data cutoff: 29 November 2023.

Conclusions

Numerically higher OS and no difference in PFS was observed with SG compared with docetaxel in the subgroups of patients with brain metastases and patients with known AGAs.

Clinical trial identification

NCT05089734.

Editorial acknowledgement

Medical writing and editorial assistance were provided by Jeffrey A. Blair, PhD, CMPP and Ebenezer Awuah-Yeboah of Ashfield MedComms, an Inizio Company, funded by Gilead Sciences, Inc.

Legal entity responsible for the study

Gilead Sciences, Inc.

Funding

Gilead Sciences, Inc.

Disclosure

E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, F. Hoffmann-La Roche, Gilead, GSK, Janssen, Merck Sharp & Dohme, Novartis, Regeneron, Turning Point, Pfizer, Genmab, Daiichi Sankyo, Johnson & Johnson, ITeos Therapeutics, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, PeerVoice, Pfizer, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme, Gilead, Novartis, Regeneron, Johnson & Johnson, Pierre Fabre; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Invited Speaker, Clinical Trial: AstraZeneca AB, AbbVie, Amgen, Bayer Consumer Care AG, Beigene, Boehringer Ingelheim GmbH, Bristol Myers Squibb International Corporation, Daiichi Sankyo Inc., Exelixis Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., GSK Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc, Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Financial Interests, Institutional, Invited Speaker: Nuvalent; Non-Financial Interests, Personal, Leadership Role, President (2021–2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Personal, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Personal, Member, Member of the Scientific Advisory Committee: CAC Hospital Universitari Parc Taulí. P. Garrido Lopez: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Janssen, MSD, Touch Expert, Medscape; Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, Janssen, Lilly, MSD, Novartis, Roche, Takeda, Daiichi Sankyo, Sanofi, Amgen; Financial Interests, Personal, Advisory Board, Spouse: Gebro, Janssen, Nordic; Financial Interests, Personal, Invited Speaker, Spouse: Janssen, Boehringer Ingelheim, Pfizer, Amgen, Nordic; Financial Interests, Personal, Other, Data monitoring committee for INC280I12201 trial in 2020: Novartis; Financial Interests, Personal, Invited Speaker, CACZ885V2201C_CANOPY-N trial: Novartis; Financial Interests, Personal, Other, Lung Cancer Medical Education TASC Committee 2021: Janssen; Financial Interests, Institutional, Invited Speaker: Novartis, Janssen, AstraZeneca, Pfizer, Blue print, Apollomics, Amgen, Array Biopharma; Financial Interests, Personal, Invited Speaker, IO102–012/KN-764 trial: IO Biotech; Financial Interests, Personal, Invited Speaker, JNJ-61186372 (JNJ-372) Clinical Development Program: Janssen; Financial Interests, Institutional, Other, Spouse: Mitsubishi, AbbVie; Financial Interests, Institutional, Other, Spouse, clinical trial team: Janssen, Boehringer; Financial Interests, Personal, Invited Speaker, JDQ443G12301 trial, Steering Committee member: Novartis; Non-Financial Interests, Personal, Leadership Role, Past Council member as Women for Oncology Committee ChairPast Fellowship and Award Committee and Press CommitteeFaculty for lung and other thoracic tumors: ESMO; Non-Financial Interests, Personal, Leadership Role, President of the Spanish Federation of Medical Societies (FACME) 2020–2022Past President 2023–2024: FACME; Non-Financial Interests, Personal, Leadership Role, Former President of Spanish Medical Oncology Society: SEOM; Non-Financial Interests, Personal, Leadership Role, Member of the Scientific Committee of the Spanish Against Cancer Research Foundation (aecc) and also Board member: AECC; Non-Financial Interests, Personal, Leadership Role, IASLC Women in Thoracic Oncology Working Group Member, Educational Committee member, Academy member: IASLC; Non-Financial Interests, Personal, Advisory Role, Member of the Spanish National Health Advisory Board: Spanish Minister of Health; Non-Financial Interests, Personal, Advisory Role, Assesmment for lung cancer screening evaluation: EUnetHTA,; Non-Financial Interests, Personal, Advisory Role: Spanish National Evaluation network (RedETS), member of the King Hussein Award’s Board of Directors; Non-Financial Interests, Personal, Advisory Role, scientific advisory group member for clinical immunological, oncology and lung cancer areas: EMA; Other, Personal, Other, My son is working with the pharma company TEVA as an engineer. I do not have any relationship with TEVA: TEVA. D. Rodriguez Abreu: Financial Interests, Personal, Advisory Board: MSD, Novartis, Roche/Genentech, Pfizer, Bristol Myers Squibb, AstraZeneca, Regeneron, Gilead, Sanofi, Amgen, Eli Lilly, Incyte, Merck Serono; Financial Interests, Personal, Invited Speaker: MSD, Novartis, Roche/Genentech, Pfizer, Bristol Myers Squibb, AstraZeneca, Regeneron, Gilead, Sanofi, Amgen, Eli Lilly, Merck Serono; Financial Interests, Personal, Other, Travel expenses: MSD, Novartis, Roche/Genentech, Pfizer. D.B. Daniel: Financial Interests, Personal, Full or part-time Employment: OneOncology; Financial Interests, Institutional, Invited Speaker: Genentech; Financial Interests, Institutional, Invited Speaker, Research payment: Daiichi Sankyo, AstraZeneca Pharma, GSK, ER Squibb, F. Hoffman La Roche, Novartis Pharmaceuticals, Array Biopharma, Amgen. T. Takahama: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Daiichi Sankyo, Pfizer, Takeda; Financial Interests, Institutional, Invited Speaker: Takeda, Pfizer. C. Chouaid: Financial Interests, Personal, Advisory Board: AZ, BI, GSK, Roche, Sanofi Aventis, BMS, MSD, Lilly, Novartis, Pfizer, Takeda, Bayer, Janssen and Amgen; Financial Interests, Institutional, Funding: AZ, BI, GSK, Roche, Sanofi Aventis, BMS, MSD, Lilly, Novartis, Pfizer, Takeda, Bayer, Janssen and Amgen. A. Rittmeyer: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Sankyo, Gilead, GSK, MSD, Eli Lilly, Novartis, Pfizer, Roche. O. Juan-Vidal: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, MSD, Roche/Genentech, AstraZeneca, Pfizer, Eli Lilly, Takeda, Janssen. A.B. Cortot: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, AstraZeneca, MSD, Pfizer, Novartis, Takeda, Roche; Financial Interests, Personal, Advisory Board: Novartis, Roche, Pfizer, Janssen, Exeliom, Amgen; Financial Interests, Institutional, Research Grant: Merck, Roche, AbbVie, Exeliom; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Janssen, Roche, Sparta, Amgen, Mirati, AbbVie; Non-Financial Interests, Personal, Member of Board of Directors: French Thoracic Intergroup. R. Patel: Financial Interests, Personal, Full or part-time Employment: Gilead Sciences, Inc; Financial Interests, Personal, Stocks/Shares: Gilead Sciences, Inc. S. Mekan: Financial Interests, Personal, Full or part-time Employment: Gilead Sciences, Inc; Financial Interests, Personal, Stocks/Shares: Gilead Sciences, Inc. N. Fernando: Financial Interests, Personal, Full or part-time Employment: Gilead Sciences, Inc; Financial Interests, Personal, Stocks/Shares: Gilead Sciences, Inc. G. Mountzios: Financial Interests, Personal, Advisory Board: Roche, BMS, Takeda, Janssen, Sanofi; Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Pfizer, Novartis, Amgen, AstraZeneca, Roche, Novartis, AstraZeneca, Lilly, GSK, Amgen, Gilead Pharmaceuticals, BMS, Boehringer Ingelheim, Amgen; Financial Interests, Institutional, Invited Speaker: MSD; Non-Financial Interests, Personal, Officer, Member of the Educational Publications Working GroupMember of the Lung Cancer Faculty: ESMO. All other authors have declared no conflicts of interest.