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NCT03260023 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE1, PHASE2
Status at capture
ACTIVE NOT RECRUITING
Registry last update
2026-02-05

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

Phase II Part 1: Overall Response Rate (ORR) by RECIST 1.1

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outcome · POSTED

Phase II Part 2 Cohort A: Progression Free Survival (PFS) by RECIST 1.1

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outcome · POSTED

Progression Free Survival (PFS) Phase II Part 2 Cohort A by Stratification

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outcome · POSTED

Overall Response Rate (ORR) by Using RECIST 1.1 : Phase Ib, Phase II Part 2 Cohort A

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outcome · POSTED

Progression Free Survival (PFS) (Phase Ib, Phase II Part 1)

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outcome · POSTED

Overall Survival (OS) : Phase Ib, Phase II Part 1, Phase II Part 2 Cohort A

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outcome · POSTED

Duration of Overall Response (DoR): Phase Ib, Phase II Part 1, Phase II Part 2 Cohort A

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outcome · POSTED

Proportion of Progressive Disease Phase II Part 2 Cohort B

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
Inclusion Criteria: * Female or male participants, aged at least 18 years (no upper limit of age) * ECOG PS 0 or 1 * Life expectancy of at least 3 months * Participants with histologically or cytologically documented metastatic or refractory/recurrent HPV-16 + cancer: cervical, vulvar, vaginal, penile and anal. * Disease MUST not be amenable to curative surgery resection or curative radiotherapy with documented disease progression * Prior therapy: * No more than one prior systemic treatment for recurrent /metastatic disease * Prior treatment for recurrent or metastatic disease is not required for: * Participants with recurrence/progression within 6 months after completion of prior multimodal therapy for localized or locally advanced disease * Participants who are unsuitable for platinum-based therapy * Participants who refuse chemotherapy or other standard therapies for the treatment of metastatic or recurrent disease * Limited hepatic disease for participants with liver metastases at baseline * Availability of tumor tissue from biopsy * At least one measurable lesion by CT scan according to RECIST 1.1. * Adequate hematological, hepatic and renal function * Negative blood pregnancy test at screening for women of childbearing potential * Highly effective contraception for both male and female participants if the risk of conception exists during the study period and for 3 months after the last study treatment administration Exclusion Criteria: * Prior exposure to cancer immunotherapy including cancer vaccines, any antibody/drug targeting T cell co-regulatory proteins (immune checkpoints) * Participants under chronic treatment with systemic corticosteroids or other immunosuppressive drugs for a period of at least 4 weeks and whose treatment was not stopped 2 weeks prior to the first study treatment, with the exception of participants with adrenal insufficiency who may continue corticosteroids at physiological replacement dose, equivalent to ≤ 10 mg prednisone daily. Steroids with no or minimal systemic effect (topical, inhalation) are allowed * Participants with CNS metastases except those with brain metastases treated locally and clinically stable during 4 weeks prior to start of study treatment, and those without ongoing neurological symptoms that are related to the brain localization of the disease * Other active malignancy requiring concurrent systemic intervention * Participants with previous malignancies other than the target malignancy to be investigated in this trial (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period * Participant with any organ transplantation, including allogeneic stem cell transplantation * Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI-CTC), any history of anaphylaxis, or uncontrolled asthma * Any known allergy or reaction to eggs, gentamycin or attributed to compounds of similar chemical or biological composition to therapeutic vaccines/immunotherapeutic products * Any known allergy or reaction to any component of anti-PD-L1/PD-1 or its excipients * Participants with known history or any evidence of active interstitial lung disease / pneumonitis * Participants with active, known, or suspected auto-immune disease or immunodeficiency, except type I diabetes mellitus, hypothyroidism only requiring hormone replacement or skin disorders (such as vitiligo, psoriasis) not requiring systemic treatment * Clinically significant (that is, active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction (\< 6 months prior to enrollment), unstable angina pectoris, congestive heart failure (New York Heart Association Classification Class ≥ II), or serious uncontrolled cardiac arrhythmia requiring medication/active intervention, history of myocarditis * History of uncontrolled intercurrent illness including but not limited to: * Hypertension uncontrolled by standard therapies (not stabilized to 150/90 mmHg or lower) * Uncontrolled diabetes (e.g., hemoglobin A1c ≥ 8%) * Uncontrolled infection
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. intervention Names
    1. Biological: TG4001
    2. Drug: Avelumab
    label
    TG4001/Avelumab
    type
    EXPERIMENTAL
  2. description
    Applicable for Phase II part 2.
    intervention Names
    1. Drug: Avelumab
    label
    Avelumab
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. TG4001/Avelumab
    description
    PhIb: Dose escalation PhII: Established RP2D for TG4001
    name
    TG4001
    type
    BIOLOGICAL
  2. arm Group Labels
    1. Avelumab
    2. TG4001/Avelumab
    description
    Anti PD-L1
    name
    Avelumab
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
143
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    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
    measure
    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
    time Frame
    From Day 1 to Day 28
  2. description
    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.
    measure
    Phase II Part 1: Overall Response Rate (ORR) by RECIST 1.1
    time Frame
    From treatment start, every 6 weeks for the first 9 months, then every 12 weeks up to 2 years.
  3. description
    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.
    measure
    Phase II Part 2 Cohort A: Progression Free Survival (PFS) by RECIST 1.1
    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.
  4. description
    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.
    measure
    Progression Free Survival (PFS) Phase II Part 2 Cohort A by Stratification
    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.
secondary Outcomes
  1. description
    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.
    measure
    Overall Response Rate (ORR) by Using RECIST 1.1 : Phase Ib, Phase II Part 2 Cohort A
    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.
  2. description
    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.
    measure
    Progression Free Survival (PFS) (Phase Ib, Phase II Part 1)
    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.
  3. description
    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.
    measure
    Overall Survival (OS) : Phase Ib, Phase II Part 1, Phase II Part 2 Cohort A
    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.
  4. description
    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.
    measure
    Duration of Overall Response (DoR): Phase Ib, Phase II Part 1, Phase II Part 2 Cohort A
    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.
  5. description
    Number of participants with liver metastases at baseline who has a documented disease progression as per RECIST1.1.
    measure
    Proportion of Progressive Disease Phase II Part 2 Cohort B
    time Frame
    From randomization: every 6 weeks up to 24 weeks.
Full study description
brief 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.
Source references
references
  1. citation
    Borcoman E, Lalanne A, Delord JP, Cassier PA, Rolland F, Salas S, Limacher JM, Capitain O, Lantz O, Ekwegbara C, Jeannot E, Cyrta J, Tran-Perennou C, Castel-Ajgal Z, Marret G, Piaggio E, Brandely M, Tavernaro A, Makhloufi H, Bendjama K, Le Tourneau C. Phase Ib/II trial of tipapkinogene sovacivec, a therapeutic human papillomavirus16-vaccine, in combination with avelumab in patients with advanced human papillomavirus16-positive cancers. Eur J Cancer. 2023 Sep;191:112981. doi: 10.1016/j.ejca.2023.112981. Epub 2023 Jul 11.
    pmid
    37506588
    type
    RESULT
Source notices and limitations
    Discovery and provenance
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    Preserved source evidence · Not medical advice