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

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

Time frame: From Day 1 to Day 28

Population: Phase Ib : All participants included and who received any amount of study treatment were included in the SAF. Any participant who was assigned a participant number, but did not receive any study treatment was not included in the SAF.~Phase II part 1 and Phase II part 2: the outcome measure safety and tolerability has not been defined as primary endpoint.~Therefore Phase II part 1 and Phase II part 2 are not included in the analysis population for safety and tolerability as primary endpoint.

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.

Time frame: From treatment start, every 6 weeks for the first 9 months, then every 12 weeks up to 2 years.

Population: Phase II part 1 (Evaluable per protocol): Participants dosed with both IMPs and with at least baseline and post-baseline evaluable CT-scan at week 6 according to RECIST 1.1 and no major inc/exc, dosing or protocol violation, except if participant progressed or died due to disease.~Phase Ib and phase II part 2: the outcome measure ORR has not been defined as primary endpoint.~Therefore Phase Ib and phase II part 2 are not included in the analysis population for ORR as primary endpoint.

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.

Time frame: From randomization: Every 6 weeks for the first 9 months, then every 12 weeks through study completion, for an average of 1 year.

Population: Phase II part 2, Cohort A: All randomized participants who were adminstered at least one dose of IMP(s) according to the treatment allocated at randomization. (FAS)~For Phase Ib, Phase II part 1 and Phase II part 2 Cohort B : the outcome measure PFS has not been defined as primary endpoint Therefore Phase Ib, Phase II part 1 and Phase II part 2 Cohort B are not included in the analysis population for PFS as primary endpoint.

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.

Time frame: From randomization: Every 6 weeks for the first 9 months, then every 12 weeks through study completion, for an average of 1 year.

Population: Phase II part 2 Cohort A: All randomized participants who were adminstered at least one dose of IMP(s) according to the treatment allocated at randomization. (FAS)~For Phase Ib, Phase II part 1 and Phase II part 2 Cohort B : the outcome measure PFS has not been defined as primary endpoint.~Therefore Phase Ib, Phase II part 1 and Phase II part 2 Cohort B are not included in the analysis population for PFS as primary endpoint.

Duration of overall response in weeks (DoR) applies only to patients whose best overall response is CR or PR. The start date is the date of first documented response (CR or PR) and the end date is the date of event defined as first documented disease progression or death due to underlying cancer.

Time frame: From treatment start Phase Ib, Phase II part 1 / from randomization Phase II part 2 Cohort A : every 6 weeks for the first 9 months, then every 12 weeks through study completion, for an average of 2.5 years.

Population: For phase Ib, phase II part 1 and phase II part 2 Cohort A, analysis population consists of all included participants who were dosed with IMP(s) according to treatment allocation and who have a confirmed response according to RECIST1.1.~For Phase II part 2 Cohort B, the outcome measure duration of overall response has not been defined as secondary endpoint. Therefore Phase II part 2 cohort B is not included in the analysis population.

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.

Time frame: From treatment start (phase Ib) / randomization (phase II part 2) : Every 6 weeks for the first 9 months, then every 12 weeks up to 2 years.

Population: For Phase Ib / Phase II part 2 Cohort A: All participants who received at least one dose of IMP(s) according to treatment allocation.~Phase II part 1 and phase II part 2 Cohort B: the outcome measure ORR has not been defined as secondary endpoint.~Therefore Phase II part 1 and phase II part 2 Cohort B are not included in the analysis population for ORR as secondary endpoint.

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 Cohort A to the date of death due to any cause. If a patient is not known to have died survival will be censored at the date of last contact.

Time frame: From treatment start : Phase Ib, Phase II part 1 / from randomization: Phase II part 2 Cohort A through study completion, for an average of 4.5 years.

Population: Phase Ib: All participants included and who received any amount of study treatment.~Phase II part 1: Evaluable participants' population. Phase II part 2 Cohort A: All randomized participants who were administered at least one dose of IMP(s) according to the treatment allocated at randomization.~For the Phase II part 2 Cohort B, the outcome measure Overall Survival has not been defined as secondary endpoint. Therefore Phase II part 2 Cohort B is not included in the analysis population.

PFS is defined as the 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. 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.

Time frame: From treatment start (phase Ib, phase II part 1): Every 6 weeks for the first 9 months, then every 12 weeks through study completion, for an average of 1 year.

Population: For Phase Ib: All participants included and who received any amount of study treatment.~For phase II part 1: Evaluable participants population (EPP)~Phase II part 2, cohort A and cohort B : the outcome measure PFS has not been defined as secondary endpoint.~Therefore Phase II part 2, cohort A and cohort B are not included in the analysis population for PFS as secondary endpoint.

Number of participants with liver metastases at baseline who has a documented disease progression as per RECIST1.1.

Time frame: From randomization: every 6 weeks up to 24 weeks.

Population: Phase II part 2 Cohort B: All randomized participants administered with at least one dose of IMP(s) according to allocation at randomization (FAS). One participant (cohort B - Avelumab) was excluded from analysis because no IMP has been administered.~Phase Ib, Phase II part 1 and Phase II part 2 Cohort A, proportion of progressive disease has not been defined as secondary endpoint. Therefore phase Ib, Phase II part 1 and Phase II part 2 Cohort A are not included in the analysis population.