Phase Ib/II of TG4001 and Avelumab in HPV16 Positive R/M Cancers Including Oropharyngeal SCCHN
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|ClinicalTrials.gov Identifier: NCT03260023|
Recruitment Status : Recruiting
First Posted : August 24, 2017
Last Update Posted : October 16, 2019
The study will consist of two parts :
In the phase Ib part: 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, evaluation of efficacy and further evaluation of safety of the combination of TG4001 and avelumab will be performed.
In both parts, tumor response will be evaluated on local assessment using RECIST 1.1.
All patients will be followed up until disease progression or death due to any cause or the date of data cut-off, whichever occurs first.
|Condition or disease||Intervention/treatment||Phase|
|Head and Neck Squamous Cell Carcinoma HPV Positive Oropharyngeal Squamous Cell Carcinoma HPV-Related Carcinoma||Biological: TG4001 Drug: Avelumab||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||52 participants|
|Intervention Model:||Single Group 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 Including Oropharyngeal Squamous Cell Carcinoma of the Head and Neck (SCCHN)|
|Actual Study Start Date :||September 11, 2017|
|Estimated Primary Completion Date :||December 2020|
|Estimated Study Completion Date :||December 2021|
PhIb Dose escalation PhII established RP2D of the combination
- 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: To evaluate the efficacy of TG4001 combined to avelumab in terms of Overall Response Rate (ORR) by using RECIST 1.1 in patients with recurrent or metastatic (R/M) HPV-16 positive advanced malignancies including oropharyngeal SCCHN. [ Time Frame: Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years ]
- Overall response rate (ORR) [ Time Frame: Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years ]Using RECIST 1.1 (phase Ib part)
- Progression Free Survival (PFS) [ 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 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 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|