723MO - Tisotumab vedotin (TV) + carboplatin (Carbo) in first-line (1L) or + pembrolizumab (Pembro) in previously treated (2L/3L) recurrent or metastatic cervical cancer (r/mCC): Interim results of ENGOT-Cx8/GOG-3024/innovaTV 205 study

Background

TV demonstrated durable activity (objective response rate [ORR]=24%; median duration of response [mDOR]=8.3 mo) with manageable safety in previously treated r/mCC (Lancet Oncol. 2021; 22:609-619). Here we report results for the 1L TV + carbo and 2L/3L TV + pembro cohorts of the 2-part, multi-cohort phase Ib/II trial ENGOT-cx8/GOG-3024/innovaTV 205 clinical trial in r/mCC.

Methods

In the 1L TV + carbo cohort, pts with no prior systemic therapy (excluding chemoradiation) for r/mCC received TV 2.0 mg/kg + carbo AUC 5 IV every 3 weeks (Q3W). In the 2L/3L TV + pembro cohort, pts with r/mCC, with disease progression on/after 1–2 prior systemic therapies, received TV 2.0 mg/kg + pembro 200 mg IV Q3W. The primary endpoint was ORR per RECIST v1.1.

Results

There were 33 pts treated with 1L TV + carbo (median 5 cycles). Confirmed ORR was 55% (Table). All treated pts had adverse events (AEs) with 76% reporting grade (gr) ≥3 AEs regardless of causality. Prespecified AEs of interest (gr 1-2/ gr ≥3) included ocular (55%/3%), peripheral neuropathy (27%/12%) and bleeding events (48%/6%). There were 35 pts treated with 2L/3L TV + pembro (median 6 cycles), with most having received 1 prior systemic treatment for r/mCC (57%) and prior bevacizumab (57%). Confirmed ORR was 35% (Table). All treated pts had AEs with 74% reporting gr ≥3 AEs regardless of causality. AEs of interest included (gr 1-2/ gr ≥3) ocular (51%/3%), peripheral neuropathy (37%/3%) and bleeding events (54%/9%). There were no treatment-related deaths in either cohort.

Conclusions

Both 1L TV + carbo and 2L/3L TV + pembro had encouraging antitumor activity with acceptable safety profiles in pts with r/mCC. Table: 723MO

Summary of efficacy

NE, not estimable. ^a1 pt was excluded from the full analysis set as they didn’t have any target or non-target lesions at baseline. Response ongoing in 13/18 pts with 1L TV + carbo and 8/12 pts with 2L/3L TV + pembro.

Clinical trial identification

NCT03786081.

Editorial acknowledgement

Editorial assistance was provided by Jerome Sah, PhD (ApotheCom, Yardley, PA, USA), and funded by Genmab A/S.

Legal entity responsible for the study

Genmab A/S and Seagen Inc.

Funding

Genmab A/S.

Disclosure

I.B. Vergote: Financial Interests, Institutional, Advisory Role, Consultancy fees: Clovis Oncology, Carrick Therapeutics, Deciphera Pharmaceuticals, Elevar Therapeutics, Genmab, Amgen, Millennium Pharmaceuticals, Octimet Oncology, Verastem Oncology; Financial Interests, Personal and Institutional, Advisory Role, Consultancy fees: AstraZeneca, F. Hoffmann-La Roche Ltd, GSK, Immunogen, MSD, Novocure, Oncoinvent, Sotio; Financial Interests, Personal, Advisory Role: Elevar Therapeutics; Financial Interests, Personal, Advisory Role: Jazz Pharma, Mersana, Zentalis; Financial Interests, Institutional, Research Grant, via KULeuven: Oncoinvent, Genmab; Financial Interests, Personal, Research Grant: Amgen, Roche; Financial Interests, Personal, Other, Accommodations/travel expenses: Amgen, MSD, Tesaro, AstraZeneca, Roche. B.J. Monk: Financial Interests, Personal, Advisory Role: Agenus, Akeso Bio, Aravive, AstraZeneca, Clovis, Eisai, Elevar, Genmab/Seagen, GOG Foundation, Gradalis, ImmunoGen, Karyopharm, Iovance, Merck, McKesson, Mersana, Novocure, Myriad, Pfizer, Puma, Roche/Genentech, Sorrento, Tesaro/GSK, VBL; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Clovis, Eisai, Merck, Roche/Genentech, Tesaro/GSK. R.E. O’Cearbhaill: Financial Interests, Personal, Other, Honoraria: GlaxoSmithKline; Financial Interests, Personal, Advisory Role: Regeneron, Seagen; Financial Interests, Institutional, Research Grant: Bayer/Celgene/Juno, Tesaro/GSK, Ludwig Cancer Institute, Abbvie/StemCentrx, Regeneron, TCR2 Therapeutics, Atara Biotherapeutics, MarkerTherapeutics, Syndax Pharmaceuticals, Genmab Therapeutics, Sellas Therapeutics, Genentech, Kite Pharma, Gynecologic Onco; Financial Interests, Personal, Other, Meal: AstraZeneca; Non-Financial Interests, Personal, Other, Non-compensated steering committee member for the PRIMA, Moonstone (Tesaro/GSK) and DUO-O (AstraZeneca) studies. S. Banerjee: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Amgen, Clovis, Genmab, Immunogen, Mersana, MSD, Merck Sereno, OncXerna, Pfizer, Roche; Financial Interests, Personal, Other, PI-pharma sponsored clinical trial: Verastem; Financial Interests, Institutional, Research Grant: AstraZeneca, Tesaro, GSK. D.C. Collins: Financial Interests, Personal, Other, Honoraria: AZD, Roche, Pfizer, Amgen, Takeda, Genmab; Financial Interests, Personal, Advisory Role: Genmab, Pfizer, MSD; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Other, Travel/accommodations/expenses: Roche. M.R. Mirza: Financial Interests, Personal, Advisory Board: AstraZeneca, Biocad, GSK, Karyopharm, Merck, Roche, Zailab; Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK; Financial Interests, Personal, Member of the Board of Directors: Karyopharm; Financial Interests, Personal, Stocks/Shares: Karyopharm; Non-Financial Interests, Institutional, Research Grant: Apexigen; Non-Financial Interests, Institutional, Research Grant: AstraZeneca; Non-Financial Interests, Institutional, Other, Trial chair: Deciphera; Non-Financial Interests, Institutional, Research Grant: GSK, Ultimovacs. D. O'Malley: Financial Interests, Personal, Advisory Role: AstraZeneca, Tesaro/GSK, Immunogen, Ambry, Janssen/J&J, BBI, Agenus, AbbVie, Regeneron, Amgen, Novocure, Genentech/Roche, GOGFoundation, Iovance Biotherapeutics, Inc, Myriad Genetics, Eisai, Agenus, Tarveda, Merck, SeaGen, Novartis, Mersana, Clovis, Rubi; Financial Interests, Institutional, Research Grant: AstraZeneca, Tesaro/GSK, Immunogen, Janssen/J&J, AbbVie, Regeneron, Amgen, Novocure, Genentech/Roche, VentiRx, Array Biopharma, EMD Serono, Ergomed, Ajinomoto Inc., Ludwig Cancer Research Stemcentrx, Inc, Cerulean Pharma, GOGFoundation, NCI, Bristol Myer. S. Pignata: Financial Interests, Personal, Other, Honoraria: Roche, AstraZeneca, MSD, Clovis, GSK; Financial Interests, Institutional, Research Grant: Roche, MSD, Pfizer, AstraZeneca. B. Melichar: Financial Interests, Personal, Other, Honoraria: Roche, Pfizer, BMS, Astellas, Novartis, Bayer, MSD, Merck Serono, Sanofi, Servier, AstraZeneca, Amgen, Janssen, Eisai, E. Lilly, Pierre Fabre; Financial Interests, Personal, Advisory Role: Roche, Pfizer, BMS, Astellas, Novartis, Bayer, MSD, Merck Serono, Sanofi, Servier, AstraZeneca, Amgen, Janssen, Eisai, E. Lilly, Pierre Fabre; Financial Interests, Personal, Other, Travel/accommodations/expenses: Merck, Serono, BMS. K.S. Tewari: Financial Interests, Institutional, Advisory Role: Genentech, Regeneron, AbbVie, Merck; Financial Interests, Personal, Advisory Role: Genentech, Merck, Instil Bio, Eisai, AstraZeneca, Clovis, GSK/Tesaro, AbbVie; Financial Interests, Personal, Speaker’s Bureau, Speaker bureau/expert testimony: Merck, Eisai, AstraZeneca, GSK/Tesaro, Clovis; Financial Interests, Personal, Leadership Role, DSMB Chair – Iovance study on TILs: Iovance. I. Soumaoro: Financial Interests, Personal, Full or part-time Employment: Genmab. C. Mondrup Andreassen: Financial Interests, Personal, Full or part-time Employment: Genmab A/S; Financial Interests, Personal, Stocks/Shares: Genmab A/S. L.V. Nicacio: Financial Interests, Personal, Full or part-time Employment: Seagen; Financial Interests, Personal, Other, Travel/accommodations/expenses: Seagen. D. Lorusso: Financial Interests, Personal, Other, Honoraria: MSD, ImmunoGen, Genmab, AstraZeneca, Merck Serono, Clovis, Pharmamar, GSK; Financial Interests, Personal, Advisory Role: Merck Serono, Pharmamar; Financial Interests, Personal, Speaker’s Bureau: Clovis; Financial Interests, Personal, Expert Testimony: Clovis; Financial Interests, Institutional, Research Grant: MSD, Clovis, GSK, Pharmamar; Financial Interests, Personal, Other, Travel/accommodations/expenses: Pharmamar, GSK, AstraZeneca, Roche; Financial Interests, Personal, Member of the Board of Directors: GCIG, MITO Group, Engot. All other authors have declared no conflicts of interest.