Phase Ib/II of TG4001 and Avelumab in HPV16 Positive R/M Cancers

Condition(s) studied

Investigational drug(s) / intervention(s)

TG4001: PhIb: Dose escalation PhII: Established RP2D for TG4001

Avelumab: Anti PD-L1

Study summary

The study will consist of two parts :

In the phase Ib: safety will be assessed in consecutive cohorts of 3 to 6 participants at increasing doses of TG4001 in combination with avelumab according to a 3+3 design. There will be no intra-participant 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 participants 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 participants with HPV-16 positive advanced malignancies.

In both phases, evaluation of tumor response will be done locally according to RECIST 1.1.

All participants will be followed up until disease progression, death, or unacceptable toxicity, or study withdrawal for any reason, whichever occurs first.

Eligibility

Primary outcome measure(s)

• Phase Ib: To Evaluate the Safety and Tolerability of the Combination of TG4001 Plus Avelumab in Participants With Recurrent or Metastatic HPV-16 Positive Advanced Malignancies — From Day 1 to 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 — From treatment start, every 6 weeks for the first 9 months, then every 12 weeks up to 2 years.
  Percentage of participants whose best overall response is either a Complete Response or a Partial Response according to Response Evaluation Criteria In Solid Tumors (RECIST v1.0) criteria over the the total number of evaluable participants. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.", or similar definition that is accurate and appropriate.
• Phase II Part 2 Cohort A: Progression Free Survival (PFS) by RECIST 1.1 — From randomization: Every 6 weeks for the first 9 months, then every 12 weeks through study completion, for an average of 1 year.
  PFS is defined as the time from the date of randomization to the date of first documented tumor progression or death due to any cause, whichever occurs first. If a participant has not had a PFS event at the cut-off date for analysis or at the date when a further antineoplastic therapy (other than those planned as study treatment in the protocol) is started, PFS will be censored at the date of last evaluable tumor assessment before the cut-off or start of further antineoplastic therapy.
• Progression Free Survival (PFS) Phase II Part 2 Cohort A by Stratification — From randomization: Every 6 weeks for the first 9 months, then every 12 weeks through study completion, for an average of 1 year.
  PFS is defined as the time from the date of randomization to the date of first documented tumor progression or death due to any cause, whichever occurs first. If a participant has not had a PFS event at the cut-off date for analysis or at the date when a further antineoplastic therapy (other than those planned as study treatment in the protocol) is started, PFS will be censored at the date of last evaluable tumor assessment before the cut-off or start of further antineoplastic therapy.

Trial sites (20)