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HPV-Related CarcinomaPhase 1/2NCT03260023

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

A Phase 1/2 study testing TG4001 and Avelumab in people with HPV-Related Carcinoma and HPV-Related Cervical Carcinoma, run by Transgene at 20 sites in 3 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
TG4001 and Avelumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
143 participants
Where
20 sitesin 3 countries
Study dates
1 Sep 2017to Dec 2026
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

20 sites in 3 countries.

20 sites in 3 countries

France12 sites

  • I.C.O. Paul Papin

    Angers

  • CHU Besançon

    Besançon

  • Hôpital Saint André - CHU de Bordeaux

    Bordeaux

  • Hôpitaux Civils de Colmar - Hôpital Pasteur

    Colmar

  • CLCC Georges-François Leclerc

    Dijon

  • Centre Léon Bérard

    Lyon

  • Hopital de la Timone

    Marseille

  • Institut Curie

    Paris

  • I.C.O. Gauducheau

    Saint-Herblain

  • Centre Paul Strauss - ICANS - Institut de cancérologie Strasbourg Europe

    Strasbourg

  • Institut Claudius Regaud - IUCT - Oncopole

    Toulouse

  • Institut Gustave Roussy

    Villejuif

Other trials in France

Spain6 sites

  • ICO Badalona - Hospital Germans Trias i Pujol

    Badalona

  • Hospital Virgen de las Nieves

    Granada

  • Fundación de Investigación biomédica H. 12 de Octubre

    Madrid

  • Fundación de Investigación Biomédica Hospital Clínico San Carlos

    Madrid

  • Hospital Virgen de La Victoria

    Málaga

  • Hospital General de Valencia

    Valencia

Other trials in Spain

United States2 sites

  • Mayo Clinic

    Jacksonville, Florida, 32224

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: A Phase Ib/II Trial Evaluating the Combination of TG4001 and Avelumab in Patients With HPV-16 Positive Recurrent or Metastatic Malignancies.

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.

Read more

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.

Being tested
TG4001, Avelumab
Keywords
Avelumab, Cancer, Anti PD-L1, Therapeutic Vaccine
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TG4001Biological

    PhIb: Dose escalation PhII: Established RP2D for TG4001

  • AvelumabDrug

    Anti PD-L1

Study groups in NCT03260023
Study groupRoleWhat they receive
TG4001/AvelumabExperimentalNot described
Receives: Biological: TG4001; Drug: Avelumab
AvelumabExperimentalApplicable for Phase II part 2.
Receives: Drug: Avelumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    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

    Measured: From Day 1 to Day 28

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

    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.

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

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

    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.

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

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

    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.

    Measured: 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 (5)

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

    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.

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

    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.

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

    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.

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

    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.

    Measured: 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. Proportion of Progressive Disease Phase II Part 2 Cohort B

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

    Measured: From randomization: every 6 weeks up to 24 weeks.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Aug 2017
  2. Study start1 Sep 2017
  3. Primary completion18 Sep 2024
  4. Study completionDec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
143 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03260023
Sponsor's protocol ID
TG4001.12
Status last verified
Jan 2026
First submitted
17 Aug 2017
Last updated
5 Feb 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 37506588

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing TG4001 and Avelumab in people with HPV-Related Carcinoma and HPV-Related Cervical Carcinoma, run by Transgene at 20 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 5 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in France, Spain, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03260023, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2026.

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