NCT04697628 · CITED IN SOURCE DOCUMENTS

Tisotumab Vedotin vs Chemotherapy in Recurrent or Metastatic Cervical Cancer

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2026-02-24

This trial is being done to find out whether tisotumab vedotin works better than chemotherapy to treat cervical cancer. People in this study have cervical cancer that has spread to other parts of the body (metastatic) or has come back after being treated (recurrent). Participants in this trial will be randomly assigned to one of two groups. One group will be treated with tisotumab vedotin. Participants in the other group will get one of five different chemotherapy drugs (topotecan, vinorelbine, gemcitabine, pemetrexed, or irinotecan). Participants and their doctors will know which group they are in. Participants in the chemotherapy group will decide with their study doctor which drug they will take.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Overall Survival

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outcome · POSTED

Progression Free Survival (PFS) as Assessed by Investigator

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outcome · POSTED

Confirmed Objective Response Rate (ORR) as Assessed by Investigator

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outcome · POSTED

Time-to-Response (TTR) as Assessed by the Investigator

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outcome · POSTED

Duration of Response (DOR) by Investigator Assessment

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outcome · POSTED

Number of Participants With Treatment Emergent Adverse Events (TEAEs)

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outcome · NOT POSTED

EuroQOL Five Dimensions Five Level (EQ-5D-5L) Index Score

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outcome · NOT POSTED

EQ-5D Visual Analog Scale (VAS) Scores

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outcome · NOT POSTED

European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Total Score

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outcome · NOT POSTED

EORTC Quality of Life Questionnaire Cervical Cancer Module (QLQ-CX24) Total Scores

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria * Has recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma, or adenosquamous histology, and: * Has experienced disease progression during or after treatment with a standard of care systemic chemotherapy doublet, or platinum-based therapy (if eligible), defined as either: * paclitaxel + cisplatin + bevacizumab + anti-PD-(L)1 agent, or * paclitaxel + carboplatin + bevacizumab + anti-PD-(L)1 agent, or * paclitaxel + topotecan/nogitecan + bevacizumab + anti-PD-(L)1 agent * Note: In cases where bevacizumab and/or anti-PD-(L)1 agent is not a standard of care therapy or the participant was ineligible for such treatment according to local standards, prior treatment with bevacizumab and/or anti-PD-(L)1 agent is not required. * Has received 1 or 2 prior systemic therapy regimens for recurrent and/or metastatic cervical cancer. Chemotherapy administered in the adjuvant or neoadjuvant setting, or in combination with radiation therapy, should not be counted as a systemic therapy regimen. Single agent therapy with an anti-PD(L)1 agent for r/mCC cancer should be counted. * Measurable disease according to RECIST v1.1 as assessed by the investigator. * Has ECOG performance status of 0 or 1 prior to randomization. * Has life expectancy of at least 3 months. Exclusion Criteria * Has primary neuroendocrine, lymphoid, sarcomatoid, or other histologies not mentioned as part of the inclusion criteria above. * Has clinically significant bleeding issues or risks. This includes known past or current coagulation defects leading to an increased risk of bleeding; diffuse alveolar hemorrhage from vasculitis; known bleeding diathesis; ongoing major bleeding; trauma with increased risk of life-threatening bleeding or history of severe head trauma or intracranial surgery within 8 weeks of trial entry. * Has any history of intracerebral arteriovenous malformation, cerebral aneurysm, or stroke (transient ischemic attack \>1 month prior to screening is allowed). * Active ocular surface disease or a history of cicatricial conjunctivitis or inflammatory conditions that predispose to cicatrizing conjunctivitis (e.g. Wagner syndrome, atopic keratoconjunctivitis, autoimmune disease affecting the eyes), ocular Stevens-Johnson syndrome or toxic epidermal necrolysis, mucus pemphigoid, and participants with penetrating ocular transplants. Cataracts alone is not an exclusion criterion. * Major surgery within 4 weeks or minor surgery within 7 days prior to the first study treatment administration. * Peripheral neuropathy ≥grade 2. * Any prior treatment with monomethyl auristatin E (MMAE)-containing drugs. There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.
gender Based: true
healthy Volunteers: false
minimum Age: 18 Years
sex: FEMALE
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Tisotumab vedotin monotherapy
intervention Names
Drug: tisotumab vedotin
label
Tisotumab vedotin
type
EXPERIMENTAL
description
Investigator's choice of one chemotherapy treatment (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed)
intervention Names
Drug: topotecan
Drug: vinorelbine
Drug: gemcitabine
Drug: irinotecan
Drug: pemetrexed
label
Chemotherapy
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Tisotumab vedotin
description
2.0 mg/kg every 3 weeks (Q3W)
name
tisotumab vedotin
other Names
TIVDAK
PF-08046057
type
DRUG
arm Group Labels
Chemotherapy
description
1 or 1.25 mg/m2 intravenous (IV) on Days 1 to 5, every 21 days
name
topotecan
type
DRUG
arm Group Labels
Chemotherapy
description
30 mg/m2 IV on Days 1 and 8, every 21 days
name
vinorelbine
type
DRUG
arm Group Labels
Chemotherapy
description
1000 mg/m2 IV on Days 1 and 8, every 21 days
name
gemcitabine
type
DRUG
arm Group Labels
Chemotherapy
description
100 or 125 mg/m2 IV weekly for 28 days, every 42 days
name
irinotecan
type
DRUG
arm Group Labels
Chemotherapy
description
500 mg/m2 IV on Day 1, every 21 days
name
pemetrexed
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 502
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Overall survival is defined as the time from the date of randomization to the date of death due to any cause. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive.
measure
Overall Survival
time Frame
From randomization to date of death due to any cause or censoring date, whichever occurred first (maximum up to 25 months)

secondary Outcomes

description
PFS per investigator was defined as the time from the date of randomization to the first documentation of disease progression (PD) as assessed by investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1, or death due to any cause, whichever occurred earlier. PD: at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). Participants without evidence of radiographic disease progression or death were censored at the date of last adequate tumor assessment prior to data cut-off date or start of new anti-cancer therapy. Participants with disease progression or death that occurred after 2 or more missed scans were censored at the last adequate tumor assessment prior to missed scans. Participants without post-baseline scan data were censored at the day of randomization.
measure
Progression Free Survival (PFS) as Assessed by Investigator
time Frame
From the date of randomization to first documentation of PD or death due to any cause, or censoring date whichever occurred first (maximum up to 25 months)
description
Confirmed objective response rate was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) per RECIST v.1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR was defined as at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The minimum criteria for stable disease (SD) duration are defined as ≥ 5 weeks after the date of randomization. For a response to be considered as confirmed, the subsequent response had to be at least 4 weeks after the initial response. Two-sided 95% exact confidence interval (CI) was computed using the Clopper-Pearson method.
measure
Confirmed Objective Response Rate (ORR) as Assessed by Investigator
time Frame
From the date of randomization until date of confirmed CR or PR (maximum up to 25 months)
description
TTR was defined as the time from the randomization date to the date of the first confirmed objective response (CR or PR that was subsequently confirmed). CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR was defined as at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
measure
Time-to-Response (TTR) as Assessed by the Investigator
time Frame
From the date of randomization to date of date of the first confirmed objective response (maximum up to 25 months)
description
DOR was defined as the time from the date of the first confirmed objective response (CR or PR that was subsequently confirmed) to the date of the first documented PD per RECIST v1.1 or death from any cause, whichever occurred first. CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR was defined as at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
measure
Duration of Response (DOR) by Investigator Assessment
time Frame
From the date of first documented response of CR or PR to the first documented PD or death from any cause, whichever occurred first (maximum up to 25 months)
description
An AE was any untoward medical occurrence in a clinical study participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.. TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment and with onset date on or before 30 days after the last dose of study treatment.
measure
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
time Frame
From start of treatment up to 30 days after last dose of study treatment (up to 25 months)
description
The EQ-5D-5L questionnaire is a 5-item self-reported measure of functioning and well-being, which assesses 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension comprises 5 levels (no problems, slight problems, moderate problems, severe problems and extreme problems). Responses to the 5 items are then converted to a weighted health state index (utility score) based on values derived from general population samples. This health utility score is between 0 and 1, where 0 is death and 1 is perfect health.
measure
EuroQOL Five Dimensions Five Level (EQ-5D-5L) Index Score
time Frame
From start of treatment until end of follow-up
description
EQ5D is a participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state) ; higher scores indicate a better health state.
measure
EQ-5D Visual Analog Scale (VAS) Scores
time Frame
From start of treatment until end of follow-up
description
The EORTC-QLQ-C30 questionnaire is composed of 30 questions for which the answers ranges either from 1 (not at all) to 4 (very much) for items 1 to 28, or from 1 (very poor) to 7 (excellent) for items 29 to 30. The EORTC QLQ-C30 scale scores will be calculated using the EORTC QLQ-C30 Scoring Manual. These include 5 functional scales, 3 symptom scales, a global health status/QoL scale, and 6 single items. Each of the multi-item scales includes a different set of items (i.e., no item occurs in more than one scale). All of the scales and single-item measures range in score from 0 to 100, with a high scale score representing a higher response level (e.g., a high level of functioning, a high QoL, or a high level of symptomatology/problems)
measure
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Total Score
time Frame
From start of treatment until end of follow-up
description
The EORTC QLQ-CX24 questionnaire is meant for use among cervical cancer participants varying in disease stage and treatment modality. The EORTC-QLQ-CX24 questionnaire is composed of 24 questions for which the answers ranged from 1 (Not at all) to 4 (Very much). Four functional scales and 5 symptom scales will be calculated using the EORTC QLQ-CX24 Scoring Manual. The 9 scores computed from the EORTC-QLQ-CX24 questionnaire will be summarized by treatment arm using descriptive statistics.
measure
EORTC Quality of Life Questionnaire Cervical Cancer Module (QLQ-CX24) Total Scores
time Frame
From start of treatment until end of follow-up

Full study description

brief Summary: This trial is being done to find out whether tisotumab vedotin works better than chemotherapy to treat cervical cancer. People in this study have cervical cancer that has spread to other parts of the body (metastatic) or has come back after being treated (recurrent). Participants in this trial will be randomly assigned to one of two groups. One group will be treated with tisotumab vedotin. Participants in the other group will get one of five different chemotherapy drugs (topotecan, vinorelbine, gemcitabine, pemetrexed, or irinotecan). Participants and their doctors will know which group they are in. Participants in the chemotherapy group will decide with their study doctor which drug they will take.

Source references

references

citation
Jordan SE, Gonzalez-Martin A, Morlock R, Hubig L, Yonemori K, Eberst L, Zikan M, Kim HS, Banerjee S, Damian F, Salutari V, Henry S, Raimondo M, Kolinsky M, Woelber L, Tromp J, Hietanen S, Nishio S, Lee JY, Manso L, Cruz F, Barraclough L, Oaknin A, Van Nieuwenhuysen E, Randall L, Lo SH, Mutebi A, Abrahami D, Leary A, Vergote I. Patient-reported outcomes with tisotumab vedotin versus chemotherapy in patients with recurrent or metastatic cervical cancer: post hoc analyses from the open-label, randomized, phase 3 ENGOT-cx12/GOG-3057/innovaTV 301 trial. Int J Gynecol Cancer. 2026 Aug 11:104947. doi: 10.1016/j.ijgc.2026.104947. Online ahead of print.
pmid
42680635
type
DERIVED
citation
Yonemori K, Nishio S, Suzuki S, Hasegawa K, Yunokawa M, Yamaguchi S, Okamoto A, Nakamura K, Kamiura S, Fujiwara K, Katsumata N, Kobayashi H, Usami T, Mochizuki A, Takehara K, Whalley E, Noguchi H, Soumaoro I, Slomovitz B, Vergote I. Tisotumab vedotin in Japanese patients with recurrent or metastatic cervical cancer: results from the innovaTV 301/ENGOT-cx12/GOG-3057 trial. Int J Gynecol Cancer. 2026 Apr;36(4):104450. doi: 10.1016/j.ijgc.2025.104450. Epub 2025 Dec 31.
pmid
41644383
type
DERIVED
citation
Vergote I, Gonzalez-Martin A, Fujiwara K, Kalbacher E, Bagameri A, Ghamande S, Lee JY, Banerjee S, Maluf FC, Lorusso D, Yonemori K, Van Nieuwenhuysen E, Manso L, Woelber L, Westermann A, Covens A, Hasegawa K, Kim BG, Raimondo M, Bjurberg M, Cruz FM, Angelergues A, Cibula D, Barraclough L, Oaknin A, Gennigens C, Nicacio L, Teng MSL, Whalley E, Soumaoro I, Slomovitz BM; innovaTV 301/ENGOT-cx12/GOG-3057 Collaborators. Tisotumab Vedotin as Second- or Third-Line Therapy for Recurrent Cervical Cancer. N Engl J Med. 2024 Jul 4;391(1):44-55. doi: 10.1056/NEJMoa2313811.
pmid
38959480
type
DERIVED