Phase 3 Randomized Open-Label Trial of Tisotumab Vedotin Versus Chemotherapy in Second- or Third-Line Recurrent or Metastatic Cervical Cancer
- Trial ID
- 2023-503813-31-01
- Protocol
- C5721002 / SGNTV-003
- Sponsor
- Seagen Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to demonstrate improvement in the **clinical efficacy** of tisotumab vedotin compared to chemotherapy in subjects with second- or third-line (2L-3L) recurrent or metastatic cervical cancer. This is clinically relevant as it aims to establish a more effective treatment option for patients who have limited therapeutic alternatives after initial treatments have failed.
Secondary objectives include:
- Further demonstrating improvement in clinical efficacy of tisotumab vedotin compared to chemotherapy in subjects with 2L-3L cervical cancer.
- Demonstrating improvement in antitumor activity of tisotumab vedotin compared to chemotherapy in subjects with 2L-3L cervical cancer.
- Characterizing the antitumor response of tisotumab vedotin and chemotherapy in participants with 2L-3L cervical cancer.
- Evaluating the safety and tolerability of tisotumab vedotin.
- Assessing health-related quality of life (HRQOL).
Participants
The clinical trial involves a total of **292 participants** diagnosed with **second- or third-line recurrent or metastatic cervical cancer**. The study population is exclusively female, with an age range of 18 years and older, as per local regulations. Participants were selected based on their medical history of cervical cancer, specifically those who have experienced disease progression during or after standard systemic therapy and are not candidates for curative therapy. The trial includes individuals with measurable disease according to RECIST v1.1 and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Participants are required to have acceptable renal, liver, and hematological function, and a life expectancy of at least three months. Lifestyle considerations include adherence to specific prohibitions and restrictions outlined in the trial protocol. The trial does not include male subjects and involves a vulnerable population, as defined by the study criteria. Key inclusion criteria also necessitate a negative serum pregnancy test for participants of childbearing potential, with a commitment to using adequate contraception during and after the trial period.
Plans and Procedures
The clinical trial is designed as a **randomized**, open-label, Phase 3 study to evaluate the efficacy of **tisotumab vedotin** compared to investigator's choice chemotherapy in patients with second- or third-line recurrent or metastatic cervical cancer. The trial aims to demonstrate an improvement in clinical efficacy, with the primary endpoint being overall survival (OS). Secondary endpoints include progression-free survival (PFS), overall response rate (ORR), time-to-response (TTR), duration of response (DOR), incidence of adverse events (AEs), and quality of life assessments using EQ-5D-3L, EQ-5D visual analog scale (VAS), EORTC-QLQ-C30, and EORTC-QLQ-CX24.
The trial is expected to commence recruitment on November 1, 2023, and is estimated to conclude by February 28, 2028. Participants will be involved in the study for the duration of their treatment period, which may vary depending on individual response and tolerance to the treatment. The study includes several key visits: an initial screening visit to confirm eligibility based on inclusion criteria such as age, disease progression, and laboratory values; regular follow-up visits to monitor treatment response and safety; and an end-of-study visit to assess final outcomes and collect data on long-term effects.
Participants may be withdrawn from the study early if they experience unacceptable toxicity, disease progression, or if they choose to withdraw consent. The trial will adhere to strict eligibility criteria, including a requirement for participants to have measurable disease according to RECIST v1.1, an ECOG performance status of 0 or 1, and a life expectancy of at least three months. Participants must also agree to use adequate contraception and refrain from breastfeeding or donating ova during and after the trial period. The study will ensure compliance with all ethical standards and regulatory requirements throughout its duration.
Treatment
The clinical trial involves the administration of several **experimental medications** and non-experimental treatments. **Irinotecan** is provided as a concentrate for solution for infusion, with a maximum daily dose of 125 mg/m². It is administered intravenously and is classified under chemotherapy. **Gemcitabine** is also used in the trial, available as a powder for solution for infusion, with a maximum daily dose of 1000 mg/m², administered intravenously as part of the chemotherapy regimen.
**Topotecan** is included as a concentrate for solution for infusion, with a maximum daily dose of 1.25 mg/m², administered intravenously. This medication is also part of the chemotherapy treatment. **Vinorelbine** is another chemotherapy agent used, provided as a concentrate for solution for infusion, with a maximum daily dose of 30 mg/m², administered intravenously.
**Pemetrexed** is administered as a powder for solution for infusion, with a maximum daily dose of 500 mg/m², delivered intravenously. It is part of the chemotherapy regimen. **Tisotumab Vedotin**, marketed as HuMax-TF-ADC, is an antibody-drug conjugate provided as a solution for infusion, with a maximum daily dose of 2.0 mg/kg, administered intravenously.
Non-experimental treatments include **Tears Naturale II**, an eye drop solution containing **Dextran 70** and **Hypromellose**, used for ocular administration. **Maxidex 0.1% w/v**, an eye drop suspension containing **Dexamethasone**, is also used for ocular administration. Additionally, **Brimonidine Tartrate 0.2% w/v** eye drops are used for ocular administration, classified under sympathomimetics in glaucoma therapy.
Participant compliance with the dosing schedules is monitored throughout the trial. The trial aims to evaluate the efficacy of these treatments in the context of second- or third-line recurrent or metastatic cervical cancer. The administration of these medications follows strict protocols to ensure safety and efficacy in the trial setting.
Efficacy
The clinical trial aims to assess the efficacy of **tisotumab vedotin** compared to chemotherapy in patients with second- or third-line recurrent or metastatic cervical cancer. The primary endpoint for evaluating efficacy is Overall Survival (OS). Secondary endpoints include Progression-Free Survival (PFS) based on the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, Confirmed Overall Response Rate (ORR), Time-to-Response (TTR), Duration of Response (DOR), and the incidence of adverse events (AEs). Additionally, patient-reported outcomes will be measured using the EQ-5D-3L index, EQ-5D visual analog scale (VAS), EORTC-QLQ-C30, and EORTC-QLQ-CX24.
Efficacy parameters will be assessed at various timepoints throughout the trial, with specific intervals determined by the study protocol. The RECIST v1.1 criteria will be employed to evaluate tumor response, and assessments will be conducted by the investigator. The collection and analysis of data will adhere to standardized procedures to ensure accuracy and reliability. The trial is designed to provide comprehensive insights into the clinical benefits of **tisotumab vedotin** in the specified patient population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age ≥18 years or considered an adult by local regulations, at time of consent.
- 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.
- 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.
- Measurable disease according to RECIST v1.1 as assessed by the investigator
- Acceptable screening laboratory values including renal function, liver function and hematological status.
- Has ECOG PS of 0 or 1 prior to randomization.
- Has life expectancy of at least 3 months.
- 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.
- Participants of childbearing potential must agree to use adequate contraception during and for 6 months after the last trial treatment administration.
- 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.
- Must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
Exclusion Criteria
- Primary neuroendocrine, lymphoid, sarcomatoid, or other histologies not mentioned in inclusion criterion 3
- Clinically significant bleeding issues or risks
- Clinically significant cardiac disease
- History of intracerebral arteriovenous malformation, cerebral aneurysm, or stroke
- 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.
- 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.
- 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.
- 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.
- 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.
- Is pregnant or intends to conceive children within 6 months of ending study treatment.
- Is breast feeding and cannot discontinue breast feeding for the duration of the study and ≥6 months after the last study treatment administration.
- 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.
- Known allergies, hypersensitivity, or intolerance to study treatment or its excipients.
- Has known psychiatric substance abuse disorders that would interfere with cooperating with the requirements of the study.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Not Recruiting | 01 Nov 2023 | 2 |
 Belgium | Not Recruiting | 01 Nov 2023 | 20 |
 Czechia | Not Recruiting | 01 Nov 2023 | 11 |
 Finland | Not Recruiting | 01 Nov 2023 | 2 |
 France | Not Recruiting | 01 Nov 2023 | 31 |
 Germany | Not Recruiting | 01 Nov 2023 | 14 |
 Hungary | Not Recruiting | 01 Nov 2023 | 18 |
 Italy | Not Recruiting | 01 Nov 2023 | 21 |
 The Netherlands | Not Recruiting | 01 Nov 2023 | — |
 Norway | Not Recruiting | 01 Nov 2023 | 2 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
VINORELBINE | Comparator | — | INTRAVENOUS USE | 30 | 999999 | SUB00069MIG |
MAXIDEX 0.1% w/v, eye drops, suspension | Other | EYE DROPS, SUSPENSION | OCULAR USE | 9999 | 9999 | PRD5005750 |
IRINOTECAN | Comparator | — | INTRAVENOUS USE | 125 | 99999 | SUB08295MIG |
GEMCITABINE | Comparator | — | INTRAVENOUS USE | 1000 | 99999 | SUB07892MIG |
PEMETREXED | Comparator | — | INTRAVENOUS USE | 500 | 999999 | SUB09655MIG |
TEARS NATURALE II, eye drops, solution. | Other | EYE DROPS, SOLUTION | OCULAR USE | 99999 | 99999 | PRD7477619 |
PEMETREXED | Comparator | — | INTRAVENOUS USE | 500 | 999999 | SUB09655MIG |
HuMax-TF-ADC | Test | SOLUTION FOR INFUSION | INTRAVENOUS ADMINISTRATION | 2.0 | 99999 | PRD952264 |
Brimonidine Tartrate 0.2% w/v Eye Drops. | Other | EYE DROPS | OCULAR USE | 99999 | 99999 | PRD377824 |
TOPOTECAN | Comparator | — | INTRAVENOUS USE | 1.25 | 9999999 | SUB11191MIG |