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.
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
- Conditions the study is for
- HPV-Related Carcinoma, HPV-Related Cervical Carcinoma, HPV-Related Anal Squamous Cell Carcinoma
- 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
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
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
United States2 sites
Mayo Clinic
Jacksonville, Florida, 32224
Mayo Clinic
Rochester, Minnesota, 55905
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.
- Conditions
- HPV-Related Carcinoma, HPV-Related Cervical Carcinoma, HPV-Related Anal Squamous Cell Carcinoma, HPV-Related Penile Squamous Cell Carcinoma, HPV-Related Vulvar Squamous Cell Carcinoma
- 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 group | Role | What they receive |
|---|---|---|
| TG4001/Avelumab | Experimental | Not described Receives: Biological: TG4001; Drug: Avelumab |
| Avelumab | Experimental | Applicable 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.
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
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.
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.
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)
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.
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.
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.
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.
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.
- First posted24 Aug 2017
- Study start1 Sep 2017
- Primary completion18 Sep 2024
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HPV-Related CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Transgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany, EMD Serono Research & Development Institute, Inc., Pfizer
- Responsible party
- Sponsor
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
- Results posted
- Yes, on ClinicalTrials.gov
- 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