A Randomized, Open-Label Trial to Compare Tisotumab Vedotin to Investigator's Choice Chemotherapy in Patients with Cervical Cancer

Phase 1

• Conditions: Second- or Third-Line Recurrent or Metastatic Cervical Cancer; MedDRA version: 21.1Level: PTClassification code 10008342Term: Cervix carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-001655-39-DE
• Lead Sponsor: Seagen Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-05-04
• Last Update Posted: 26 February 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 482

Inclusion Criteria

1.Age =18 years or considered an adult by local regulations, at time of consent.
2.Must sign an informed consent form (ICF) indicating that they understand the purpose of and procedures required for the trial and are willing to participate in the trial prior to any other trial-related assessments or procedures.
3.Has recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma, or adenosquamous histology, and:
a.Has experienced disease progression during or after treatment with standard of care systemic therapy 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
b.Has received 1 or 2 prior systemic therapy regimens for recurrent and/or metastatic cervical cancer.
c.Is not a candidate for curative therapy, including but not limited to radiotherapy or exenterative surgery.
4. Measurable disease according to RECIST v1.1 as assessed by the investigator
5.Acceptable screening laboratory values including renal function, liver function and hematological status.
6.Has ECOG PS of 0 or 1 prior to randomization.
7. Has life expectancy of at least 3 months.
8.Has a negative serum pregnancy test for female subjects of reproductive potential. Subjects that are postmenopausal or permanently sterilized can be considered as not having reproductive potential.
9.Subjects of reproductive potential must agree to use adequate contraception during and for 6 months after the last trial treatment administration.
10. Must agree not to breastfeed or donate ova, starting at the time of informed consent and continuing through 6 months after receiving the last dose of study drug administration.
11.Where required by local health authorities, has negative serology for hepatitis B surface antigen (HBsAg)/HBV DNA, or hepatitis C antibody (HCVAb) or RNA. Active hepatitis C is defined by a known positive HCVAb result and known quantitative HCV RNA results greater than the lower limits of detection of the assay.
12.Must provide a fresh or archival biopsy prior to the first planned administration of trial treatment, unless determined it is unfeasible after sponsor medical review.
13. Must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 386
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 96

Exclusion Criteria

1. Primary neuroendocrine, lymphoid, sarcomatoid, or other histologies
not mentioned in inclusion criterion 3
2. Clinically significant bleeding issues or risks
3. Clinically significant cardiac disease
4. History of intracerebral arteriovenous malformation, cerebral
aneurysm, or stroke
5. Ocular surface disease Common Terminology Criteria for Adverse
Events (CTCAE) grade 2 or above, any prior episode of cicatricial
conjunctivitis, or any prior episode of Stevens-Johnson syndrome.
6.Other cancer: known past or current malignancy other than inclusion
diagnosis. Exceptions are malignancies with a negligible risk of
metastasis or death (e.g., 5year OS =90%) such as non-invasive basal
cell or squamous cell skin carcinoma; non-invasive, superficial bladder
cancer, and ductal carcinoma in situ.
7. Brain metastases are allowed if the following criteria are met:
definitive therapy (eg, surgery or stereotactic brain radiotherapy) has
been completed >8 weeks before the first dose of study treatment; no
evidence of clinical or radiologic progression of the brain metastases;
participant has completed perioperative corticosteroid therapy or steroid
taper.
8.Surgery/procedures: major surgery within 4 weeks or minor surgery
within 7 days prior to the first trial treatment administration. Subjects
must have recovered adequately from the toxicity or complications from
the intervention prior to starting trial treatment. Subjects who have
planned major surgery during the treatment period must be excluded
from the trial.
9.Peripheral neuropathy =grade 2.
10.Prior anti-cancer therapy:
a.Any prior treatment with MMAE-derived drugs.
b.Radiotherapy within 21 days prior to the first administration of trial
treatment. Subjects must have recovered from all clinically significant
radiation-related toxicities. At least 42 days must have elapsed from the
last administration of chemo radiotherapy.
c. Is currently participating in or has participated in a trial of an
investigational agent or device and received active treatment within
28days prior to the first dose of trial treatment.
11. Other:
a. Ongoing significant, uncontrolled medical condition.
b. Clinically significant active viral, bacterial, or fungal infection
requiring IV or oral treatment with antimicrobial therapy ending <7 days
prior to first study treatment administration.
c. Clinically relevant bilateral hydronephrosis which cannot be alleviated
by ureteral stents or percutaneous drainage.
d. Participants with clinical symptoms or signs of gastrointestinal
obstruction and who require parenteral hydration or nutrition at the time
of the first dose of study treatment.
12. Has known seropositivity of human immunodeficiency virus (HIV);
known medical history of hepatitis B or C infection. Note: No testing for
HIV, hepatitis B, or hepatitis C is required, unless mandated by local
health authorities. Exceptions include latent or controlled HIV infection.
13. Has a diagnosis of immunodeficiency or is receiving systemic steroid
therapy (dose exceeding 10 mg daily of prednisone or equivalent) or any
other form of immunosuppressive therapy within 7 days prior to the first
dose of tisotumab vedotin.
14. Is pregnant or intends to conceive children within 6 months of
ending study treatment.
15. Is breast feeding and cannot discontinue breast feeding for the
duration of the study and =6 months after the last study treatment
administration.
16. Any condition for which, in the opinion of the investigator,
participati

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate improvement in clinical efficacy of tisotumab vedotin compared to chemotherapy in subjects with second- or third-line (2L-3L) cervical cancer;Secondary Objective: • To further demonstrate improvement in clinical efficacy of tisotumab vedotin compared to chemotherapy in subjects with 2L-3L cervical cancer<br>• To demonstrate improvement in antitumor activity of tisotumab vedotin compared to chemotherapy in subjects with 2L-3L cervical cancer<br>• To characterize the antitumor response of tisotumab vedotin and chemotherapy in participants with 2L-3L cervical cancer<br>• To evaluate the safety and tolerability of tisotumab vedotin<br>• To assess health-related quality of life (HRQOL);Primary end point(s): Overall Survival (OS);Timepoint(s) of evaluation of this end point: interim analysis (IA) and final analysis (FA)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Progression-free survival (PFS) based on Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 as assessed by the investigator<br>•Confirmed overall response rate (ORR) based on RECIST v1.1 as assessed by the investigator<br>• Time-to-response (TTR) as assessed by the investigator<br>• DOR as assessed by the investigator<br>•Incidence of adverse events (AEs)<br>•EQ-5D-3L index<br>•EQ-5D visual analog scale (VAS)<br>•EORTC-QLQ-C30<br>•EORTC-QLQ-CX24;Timepoint(s) of evaluation of this end point: interim analysis (IA) and final analysis (FA)