Phase Ib/II of TG4001 and Avelumab in HPV16 Positive R/M Cancers
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|ClinicalTrials.gov Identifier: NCT03260023|
Recruitment Status : Recruiting
First Posted : August 24, 2017
Last Update Posted : February 15, 2022
The study will consist of two parts :
In the phase Ib: safety will be assessed in consecutive cohorts of 3 to 6 patients at increasing doses of TG4001 in combination with avelumab according to a 3+3 design. There will be no intra-patient dose escalation.
In the phase II part 1, evaluation of efficacy and further evaluation of safety of the combination of TG4001 and avelumab will be performed in a single arm of patients with recurrent or metastatic HPV-16 positive advanced malignancies.
In the phase II part 2, evaluation of efficacy of the combination of TG4001 and avelumab will be performed in a randomized, open-label controlled study comparing TG4001 in combination with avelumab to avelumab alone in patients with HPV-16 positive advanced malignancies.
In both phases, tumor response will be evaluated on local assessment using RECIST 1.1.
All patients will be followed up until disease progression, death, or unacceptable toxicity, or study withdrawal for any reason, whichever occurs first.
|Condition or disease||Intervention/treatment||Phase|
|HPV-Related Carcinoma HPV-Related Cervical Carcinoma HPV-Related Anal Squamous Cell Carcinoma HPV-Related Penile Squamous Cell Carcinoma HPV-Related Vulvar Squamous Cell Carcinoma||Biological: TG4001 Drug: Avelumab||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||150 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase Ib/II Trial Evaluating the Combination of TG4001 and Avelumab in Patients With HPV-16 Positive Recurrent or Metastatic Malignancies.|
|Actual Study Start Date :||September 11, 2017|
|Estimated Primary Completion Date :||December 2023|
|Estimated Study Completion Date :||December 2024|
PhIb: Dose escalation PhII: Established RP2D for TG4001
Applicable for Phase II part 2.
- Phase Ib: To evaluate the safety and tolerability of the combination of TG4001 plus avelumab in patients with recurrent or metastatic HPV-16 positive advanced malignancies [ Time Frame: Day 28 ]
Dose limiting toxicities (DLTs) includes the following:
- Grade ≥ 3 drug related adverse event (AEs). However, fatigue, nausea/vomiting adequately treated with anti-emetics, endocrinopathies adequately controlled with one physiologic hormone replacement, skin toxicity and single laboratory values out of normal range without any clinical correlate, asymptomatic grade ≥3 lipase or amylase elevation, tumor flare defined as local pain, irritation, or rash localized at sites of known or suspected tumor or a transient Grade 3 infusion adverse event are excluded.
Liver function test abnormality:
- AST or ALT > 5 x ULN
- Total bilirubin > 3 x ULN
- Concurrent AST or ALT > 3 x ULN and total bilirubin > 2 x ULN
- Drug related AE requiring treatment interruption for more than 2 weeks
- Phase II part 1: Overall Response Rate (ORR) by RECIST 1.1 [ Time Frame: Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years ]Percentage of patients whose best overall response is either a Complete Response or a Partial Response according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria over the the total number of evaluable patients.
- Phase II part 2: Progression Free Survival (PFS) by RECISIT 1.1 [ Time Frame: Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years ]Time from the date of randomization to death due to any cause, whichever occurs first.
- Overall Response Rate (ORR) by using RECIST 1.1 (phase Ib, phase II part 2) [ Time Frame: Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years ]Percentage of patients whose best overall response is either a Complete Response or a Partial Response according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria over the the total number of evaluable patients
- Progression Free Survival (PFS) (phase Ib, Phase II part 1) [ Time Frame: Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years ]Time from the date of first study treatment administration (Phase IB, Phase II Part1) to the date of first documented tumor progression or death due to any cause, whichever occurs first.
- Overall Survival (OS) [ Time Frame: Every 3 months and up to 3 years ]Time from the date of first study treatment administration (Phase Ib, Phase II part 1) or time from the date of randomization (Phase II part 2) to the date of death due to any cause.
- Duration of overall Response (DoR) [ Time Frame: Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years ]Time from first documented response (CR or PR) until documented disease progression or death, whichever occurs first.
- Disease control rate (DCR) [ Time Frame: Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years ]Proportion of patients whose best overall response is either CR, PR, or SD.
- Incidence of Adverse Event reported per CTCAE v4.03 [ Time Frame: up to 90 days after last study treatment administration ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03260023
|Contact: Transgene EU, Clinical Operations Department||+ 33 (0) 3 88 27 91 firstname.lastname@example.org|
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