Efficacy and safety of tisotumab vedotin (HuMax®-TF-ADC) monotherapy and in combination in recurrent or Stage IVB cervical cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Genmab A/S

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Mar 2019 → 19 Mar 2026

Decision date (initial)

2024-04-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-508832-68-00

EudraCT number

2017-004758-40

ClinicalTrials.gov

NCT03786081

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy

Dose escalation: to establish the maximum tolerated Dose(MTD) and RP2D of tisotumab vedotin in combination in subjects with advanced cervical cancer
Dose expansion: Evaluate the antitumor activity of tisotumab vedotin monotherapy and in combination in subjects with cervical cancer.

Secondary objectives 4

1. Assess safety and tolerability of tisotumab vedotin monotherapy and in combination
2. Evaluate durability of response of tisotumab vedotin monotherapy and in combination
3. Evaluate clinical efficacy with tisotumab vedotin monotherapy and in combination
4. To evaluate the PK and immunogenicity of tisotumab vedotin monotherapy and in combination

Conditions and MedDRA coding

Recurrent or stage IVB cervical cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Must have squamous, adenosquamous, or adenocarcinoma of the cervix and progressed on or after SOC treatments or are ineligible or intolerant to SOC for recurrent or stage IVB cervical cancer. (Arms A, B, and C only).
2. Criterion revised per Amendment 6&7. Must have squamous, adenosquamous, or adenocarcinoma of the cervix and must not have received prior systemic therapy for recurrent or stage IVB cervical cancer (Arms D, E and H).
3. Must have squamous, adenosquamous, or adenocarcinoma of the cervix and progressed on or after at least one but no more than 2 prior systemic therapies for recurrent or stage IVB cervical cancer (Arms F and Arm G only).
4. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (All Arms).
5. Is not pregnant, breastfeeding, or expecting to conceive children within the projected duration of the trial and for at least 6 months after the last trial treatment administration. A WOCBP must agree to use adequate contraception during and for 6 months after the last dose of trial treatment administration (all arms).
6. Must sign an informed consent form (ICF) indicating the trial subject understands the purpose of and procedures required for the trial and are willing to participate in the trial (All Arms).

Exclusion criteria 8

1. Has clinically relevant bilateral hydronephrosis which cannot be alleviated by ureteral stents or percutaneous drainage. (All Arms)
2. 2- Has clinical signs or symptoms of gastrointestinal obstruction and requires parenteral hydration and/or nutrition. Post operative obstructions within 4 weeks of abdominal surgery are permitted. (All Arms)
3. 3- Has Clinically significant bleeding issues or risks. Prior history (within 3 months) or current evidence of hemoptysis (1/2 teaspoon or more) ( Arm A and bevacizumab-eligible participants in Arm H)
4. 4- Recent (within 4 weeks of first dose of trial treatment) clinically significant gastrointestinal or vaginal bleeding requiring PRBC transfusion (Arm A and Bev eligible Arm H only)
5. 5- Recent (within 4 weeks of first dose of trial treatment) evidence of wound healing complications that require medical intervention (Arm A and Bev eligible Arm H only)
6. 6- Has active ocular surface disease at baseline. Subjects with prior history of cicatricial conjunctivitis are ineligible (All Arms).
7. 7-Clinically significant cardiac disease
8. 8-Requires anti-coagulation therapy (Arms A and H only

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Dose escalation: Incidences of dose-limiting toxicities (DLTs), adverse events (AEs), serious adverse events (SAEs), infusion-related AEs, Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3 AEs, and AEs related to trial treatment during the trial
2. Dose Expansion: ORR per RECIST v1.1

Secondary endpoints 7

1. AEs and evaluation of safety laboratory parameters
2. Objective Response Rate (ORR) per RECIST v1.1 (only dose escalation)
3. DOR per RECIST v1.1
4. TTR per RECIST v1.1
5. PFS per RECIST v1.1
6. Overall Survival (OS)
7. PK-concentrations and anti-drug antibodies (ADAs) associated with tisotumab vedotin

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Genmab A/S

Sponsor organisation

Genmab A/S

Address

Carl Jacobsens Vej 30

City

Valby

Postcode

2500

Country

Denmark

Scientific contact point

Organisation

Genmab A/S

Contact name

Genmab Trial Information

Public contact point

Organisation

Genmab A/S

Contact name

Genmab Trial Information

Third parties 11

Locations

6 EU/EEA countries · 17 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 50 files

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

Application history

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