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Clinical Trial
. 2023 Dec 20;41(36):5536-5549.
doi: 10.1200/JCO.23.00720. Epub 2023 Aug 31.

Tisotumab Vedotin in Combination With Carboplatin, Pembrolizumab, or Bevacizumab in Recurrent or Metastatic Cervical Cancer: Results From the innovaTV 205/GOG-3024/ENGOT-cx8 Study

Ignace Vergote  1 , Els Van Nieuwenhuysen  1 , Roisin E O'Cearbhaill  2 , Anneke Westermann  3 , Domenica Lorusso  4 , Sharad Ghamande  5 , Dearbhaile C Collins  6 , Susana Banerjee  7 , Cara A Mathews  8 , Christine Gennigens  9 , David Cibula  10 , Krishnansu S Tewari  11 , Kristine Madsen  12 , Fatih Köse  13 , Amanda L Jackson  14 , Ingrid A Boere  15 , Giovanni Scambia  16 , Leslie M Randall  17 , Azmat Sadozye  18 , Jean-François Baurain  19 , Eelke Gort  20 , Michal Zikán  21 , Hannelore G Denys  22 , Nelleke Ottevanger  23 , Frédéric Forget  24 , Camilla Mondrup Andreassen  25 , Lamar Eaton  26 , Michael J Chisamore  27 , Leonardo Viana Nicacio  28 , Ibrahima Soumaoro  26 , Bradley J Monk  29
Affiliations
Clinical Trial

Tisotumab Vedotin in Combination With Carboplatin, Pembrolizumab, or Bevacizumab in Recurrent or Metastatic Cervical Cancer: Results From the innovaTV 205/GOG-3024/ENGOT-cx8 Study

Ignace Vergote et al. J Clin Oncol. .

Abstract

Purpose: Tissue factor is highly expressed in cervical carcinoma and can be targeted by tisotumab vedotin (TV), an antibody-drug conjugate. This phase Ib/II study evaluated TV in combination with bevacizumab, pembrolizumab, or carboplatin for recurrent or metastatic cervical cancer (r/mCC).

Methods: This open-label, multicenter study (ClinicalTrials.gov identifier: NCT03786081) included dose-escalation arms that assessed dose-limiting toxicities (DLTs) and identified the recommended phase II dose (RP2D) of TV in combination with bevacizumab (arm A), pembrolizumab (arm B), or carboplatin (arm C). The dose-expansion arms evaluated TV antitumor activity and safety at RP2D in combination with carboplatin as first-line (1L) treatment (arm D) or with pembrolizumab as 1L (arm E) or second-/third-line (2L/3L) treatment (arm F). The primary end point of dose expansion was objective response rate (ORR).

Results: A total of 142 patients were enrolled. In dose escalation (n = 41), no DLTs were observed; the RP2D was TV 2 mg/kg plus bevacizumab 15 mg/kg on day 1 once every 3 weeks, pembrolizumab 200 mg on day 1 once every 3 weeks, or carboplatin AUC 5 on day 1 once every 3 weeks. In dose expansion (n = 101), the ORR was 54.5% (n/N, 18/33; 95% CI, 36.4 to 71.9) with 1L TV + carboplatin (arm D), 40.6% (n/N, 13/32; 95% CI, 23.7 to 59.4) with 1L TV + pembrolizumab (arm E), and 35.3% (12/34; 19.7 to 53.5) with 2L/3L TV + pembrolizumab (arm F). The median duration of response was 8.6 months, not reached, and 14.1 months, in arms D, E, and F, respectively. Grade ≥3 adverse events (≥15%) were anemia, diarrhea, nausea, and thrombocytopenia in arm D and anemia in arm F (none ≥15%, arm E).

Conclusion: TV in combination with bevacizumab, carboplatin, or pembrolizumab demonstrated manageable safety and encouraging antitumor activity in treatment-naive and previously treated r/mCC.

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Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Bradley J. Monk

Leadership: US Oncology

Honoraria: Agenus, Akeso Biopharma, Amgen, Aravive, AstraZeneca, Clovis Oncology, Eisai, Genmab/Seattle Genetics, ImmunoGen, Iovance Biotherapeutics, Merck, Mersana, Pfizer, Puma Biotechnology, Regeneron, Roche/Genentech, Tesaro/GSK, Vascular Biogenics, GOG Foundation, Elevar Therapeutics, Novocure, Gradalis, Karyopharm Therapeutics, Bayer, EMD Serono/Merck, Sorrento Therapeutics, US Oncology, Myriad Pharmaceuticals, Novartis, OncoC4, Pieris Pharmaceuticals, Acrivon Therapeutics, Adaptimmune, HenRui, Laekna Health Care, Panavance Therapeutics, Verastem, Zentalis

Consulting or Advisory Role: Agenus, Akeso Biopharma, Amgen, Aravive, AstraZeneca, Clovis Oncology, Eisai, Genmab/Seattle Genetics, GOG Foundation, ImmunoGen, Iovance Biotherapeutics, Merck, Mersana, Myriad Pharmaceuticals, Pfizer, Puma Biotechnology, Regeneron, Roche/Genentech, Tesaro/GSK, Vascular Biogenics, Gradalis, Karyopharm Therapeutics, Sorrento Therapeutics, Novocure, Bayer, Elevar Therapeutics, EMD Serono/Merck, Gradalis, US Oncology, Novartis, Pieris Pharmaceuticals, OncoC4, Adaptimmune, HenRui, Laekna Health Care, Panavance Therapeutics, Verastem, Zentalis

Speakers' Bureau: Roche/Genentech, AstraZeneca, Clovis Oncology, Eisai, Tesaro/GSK, Merck

Research Funding: Novartis (Inst), Amgen (Inst), Genentech (Inst), Lilly (Inst), Janssen (Inst), Array BioPharma (Inst), Tesaro (Inst), Morphotek (Inst), Pfizer (Inst), Advaxis (Inst), AstraZeneca (Inst), Immunogen (Inst), Regeneron (Inst), Nucana (Inst)

No other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
CONSORT diagram. aData cutoff date for the dose-escalation arms was January 25, 2022. bData cutoff date for the dose-expansion arms was June 20, 2022. cOne patient received brentuximab and was not analyzed for efficacy. dOne patient did not have measurable disease at baseline and was not analyzed for efficacy. 1L, first-line; 2L, second-line; 3L, third-line; PD, progressive disease; TV, tisotumab vedotin.
FIG 2.
FIG 2.
Efficacy outcomes in patients with r/mCC treated 1L with TV + carboplatin in the dose-expansion part (arm D). (A) Waterfall plot showing the maximum percentage change in target lesions. The dashed line indicates a 30% reduction from baseline. (B) Kaplan-Meier–estimated duration of response among the 18 patients with confirmed responses. (C) Kaplan-Meier–estimated overall survival. At data cutoff (June 20, 2022), the median follow-up was 17.8 months (range, 1-26). 1L, first-line; NR, not reached; OS, overall survival; r/mCC, recurrent or metastatic cervical cancer; TV, tisotumab vedotin.
FIG 3.
FIG 3.
Efficacy outcomes in patients with r/mCC treated 1L with TV + pembrolizumab in the dose-expansion arm E. (A) Waterfall plot showing the maximum percentage change in target lesions. The dashed line indicates a 30% reduction from baseline. (B) Kaplan-Meier–estimated duration of response among the 13 patients with confirmed responses. (C) Kaplan-Meier–estimated overall survival. At data cutoff (June 20, 2022), the median follow-up was 21.7 months (range, 1-29). 1L, first-line; NR, not reached; OS, overall survival; r/mCC, recurrent or metastatic cervical cancer; TV, tisotumab vedotin.
FIG 4.
FIG 4.
Efficacy outcomes in patients with r/mCC treated 2L or 3L with TV + pembrolizumab in the dose-expansion arm F. (A) Waterfall plot showing the maximum percentage change in target lesions. The dashed line indicates a 30% reduction from baseline. (B) Kaplan-Meier–estimated duration of response among the 12 patients with confirmed responses. (C) Kaplan-Meier–estimated overall survival. At data cutoff (June 20, 2022), the median follow-up was 15.0 months (range, 1-29). 2L, second line; 3L, third line; NR, not reached; OS, overall survival; r/mCC, recurrent or metastatic cervical cancer; TV, tisotumab vedotin.
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