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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Seagen Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Sep 2021 → 15 Jan 2026

Decision date (initial)

2023-12-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Seagen Inc.

External identifiers

EU CT number

2023-503813-31-01

EudraCT number

2019-001655-39

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Efficacy, Pharmacokinetic, Safety

To demonstrate improvement in clinical efficacy of tisotumab vedotin compared to chemotherapy in subjects with second- or third-line (2L-3L) cervical cancer

Secondary objectives 5

1. To further demonstrate improvement in clinical efficacy of tisotumab vedotin compared to chemotherapy in subjects with 2L-3L cervical cancer
2. To demonstrate improvement in antitumor activity of tisotumab vedotin compared to chemotherapy in subjects with 2L-3L cervical cancer
3. To characterize the antitumor response of tisotumab vedotin and chemotherapy in participants with 2L-3L cervical cancer
4. To evaluate the safety and tolerability of tisotumab vedotin
5. To assess health-related quality of life (HRQOL)

Conditions and MedDRA coding

Second- or Third-Line Recurrent or Metastatic Cervical Cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. 1. Age ≥18 years or considered an adult by local regulations, at time of consent.
2. 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. 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. 4. Measurable disease according to RECIST v1.1 as assessed by the investigator
5. 5. Acceptable screening laboratory values including renal function, liver function and hematological status.
6. 6. Has ECOG PS of 0 or 1 prior to randomization.
7. 7. Has life expectancy of at least 3 months.
8. 8. Has a negative serum pregnancy test for participants of childbearing potential. Participants that are postmenopausal or permanently sterilized can be considered as not having chilbearing potential.
9. 9. Participants of childbearing potential must agree to use adequate contraception during and for 6 months after the last trial treatment administration.
10. 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. 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. 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. 13. Must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.

Exclusion criteria 18

1. 1. Primary neuroendocrine, lymphoid, sarcomatoid, or other histologies not mentioned in inclusion criterion 3
2. 2. Clinically significant bleeding issues or risks
3. 3. Clinically significant cardiac disease
4. 4. History of intracerebral arteriovenous malformation, cerebral aneurysm, or stroke
5. 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. 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. 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. 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. 9.Peripheral neuropathy ≥grade 2.
10. 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. 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. 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 for the global portion of the study.
13. 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. 14. Is pregnant or intends to conceive children within 6 months of ending study treatment.
15. 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. 16. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise well-being) or that could prevent, limit, or confound the protocol-specified assessments.
17. 17. Known allergies, hypersensitivity, or intolerance to study treatment or its excipients.
18. 18. Has known psychiatric substance abuse disorders that would interfere with cooperating with the requirements of the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall Survival (OS)

Secondary endpoints 9

1. 1. Progression-free survival (PFS) based on Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 as assessed by the investigator
2. 2. Confirmed overall response rate (ORR) based on RECIST v1.1 as assessed by the investigator
3. 3. Time-to-response (TTR) as assessed by the investigator
4. 4. DOR as assessed by the investigator
5. 5. Incidence of adverse events (AEs)
6. 6. EQ-5D-3L index
7. 7. EQ-5D visual analog scale (VAS)
8. 8. EORTC-QLQ-C30
9. 9. EORTC-QLQ-CX24

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 6

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Seagen Inc.

Sponsor organisation

Seagen Inc.

Address

21823 30th Drive Southeast

City

Bothell

Postcode

98021-3907

Country

United States

Scientific contact point

Organisation

Seagen Inc.

Contact name

Medical monitor

Public contact point

Organisation

Seagen Inc.

Contact name

Irina Stratila

Third parties 9

Locations

13 EU/EEA countries · 47 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 103 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications