Phase II Bintrafusp alfa Monotherapy in Platinum-Experienced Cervical Cancer

Phase 1

• Conditions: Cervical Cancer; MedDRA version: 21.1Level: LLTClassification code 10008229Term: Cervical cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-003583-40-ES
• Lead Sponsor: Merck Healthcare KGaA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-05-07
• Last Update Posted: 8 June 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 135

Inclusion Criteria

1. Study participants are = 18 years of age at the time of signing the informed consent. In Japan, if a participant is at least 18 but < 20 years of age, written informed consent from his/her parent or guardian will be required in addition to the participant’s written consent.
2. Participants have a histologically documented advanced unresectable and/or metastatic cervical cancer (squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma) with disease progression during or after the prior platinum-containing chemotherapy:
a. The prior platinum-containing chemotherapy may be a systemic treatment for metastatic disease or in the adjuvant or neo-adjuvant setting. There is no limit to the number of lines of prior systemic therapy.
b. Participants who were intolerant to or ineligible for platinum-based chemotherapy are also eligible. All other inclusion/exclusion criteria (e.g. lab results) must still be met at study entry.
c. Participants must be naïve to checkpoint inhibitors as described in Section 5.2 of the Protocol.
3. Measurable disease outside the CNS according to RECIST 1.1 at Screening. Evidence of measurable disease outside the CNS must be confirmed by IRC prior to start of treatment.
Note: Lesions within the CNS are to be considered as non-target lesions only. Lesions may be considered measurable regardless of prior irradiation. Target lesions should preferably be selected from areas that have not been irradiated, or appear not to have been irradiated,
If necessary, target lesion may be selected from areas that have been, or appear to have been irradiated in the opinion of the assessor.
4. Archival tumor tissue sample or newly obtained (preferred) core or excisional biopsy of a tumor lesion is mandatory and collected during the Screening period prior to enrollment.
Fine needle aspirates are not acceptable.Tumor material must be suitable for biomarker assessment as described in the Laboratory Manual. If participant received local therapy
(e.g., radiation therapy or chemoradiotherapy) after the archival tissue was taken, a new, acceptable biopsy will be required prior to study entry.
5. Have Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1 at study entry and Day 1 of treatment with bintrafusp alfa.
6. Life expectancy = 12 weeks as judged by the Investigator.
7. Have adequate organ function: (as defined in Section 5.1)
8. Participants with known HIV infections are in general eligible if the following criteria are met (FDA Guidance on Cancer Clinical Trial Eligibility, March 2019): (as defined in Section 5.1)
9. Participants with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections are in general eligible if the following criteria are met (FDA Guidance on Cancer Clinical Trial Eligibility, March 2019):(as defined in Section 5.1)
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 122
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 13

Exclusion Criteria

1. Participants with active central nervous system (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention are excluded. Participants with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 4 weeks, and are not using steroids for at least 7 days prior to the start of study treatment. NB Lesions in the CNS at baseline must be assessed as non-target lesions only.
2. Participants with interstitial lung disease or has had a history of pneumonitis that has required oral or intravenous (IV) steroids.
3. Participants with significant acute or chronic infections.
4. Participants with active autoimmune disease that might deteriorate when receiving an immunostimulatory agent.
5. Participants with clinically significant cardiovascular/cerebrovascular disease including: cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure, or serious cardiac arrhythmia.
- Other protocol defined exclusion criteria could apply.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: -To evaluate clinical efficacy of bintrafusp alfa based on ORR;Secondary Objective: -To evaluate clinical efficacy of bintrafusp alfa based on DOR<br>-To evaluate clinical efficacy of bintrafusp alfa based on DRR<br>-To evaluate clinical safety of bintrafusp alfa<br>-To evaluate clinical efficacy based on PFS<br>-To evaluate ORR, DOR, DRR, and PFS by Investigator read<br>- To evaluate clinical efficacy based on OS<br>- To characterize the PK profile of bintrafusp alfa<br>- To characterize the immunogenicity of bintrafusp alfa<br>- To evaluate clinical efficacy of bintrafusp alfa according to PD-L1 expression;Primary end point(s): - Confirmed objective response according to RECIST 1.1 assessed by an IRC;Timepoint(s) of evaluation of this end point: Time from first treatment to planned final assessment at approximately 2 years.