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

NCT03260023 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 1 other identifier: TG4001.12
• Study Type: interventional
• Target: 143
• Locations: 3 countries
• Sites: 20

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.

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

Keywords

Avelumab; Cancer; Anti PD-L1; Therapeutic Vaccine

Outcome Measures

Primary Outcomes (4)

• 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

  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.

  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.

  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.

  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

  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)

  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

  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

  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

  From randomization: every 6 weeks up to 24 weeks.

Study Arms (2)

TG4001/Avelumab

EXPERIMENTAL

Biological: TG4001; Drug: Avelumab

Avelumab

EXPERIMENTAL

Applicable for Phase II part 2.

Drug: Avelumab

Interventions

TG4001 BIOLOGICAL

PhIb: Dose escalation PhII: Established RP2D for TG4001

TG4001/Avelumab

Avelumab DRUG

Anti PD-L1

Avelumab; TG4001/Avelumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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%)

Sponsors & Collaborators

• Transgene: lead
• Merck KGaA, Darmstadt, Germany: collaborator
• EMD Serono Research & Development Institute, Inc.: collaborator
• Pfizer: collaborator

Study Sites (20)

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

I.C.O. Paul Papin

Angers, France

Location

CHU Besançon

Besançon, France

Location

Hôpital Saint André - CHU de Bordeaux

Bordeaux, France

Location

Hôpitaux Civils de Colmar - Hôpital Pasteur

Colmar, France

Location

CLCC Georges-François Leclerc

Dijon, France

Location

Centre Léon Bérard

Lyon, France

Location

Hopital de la Timone

Marseille, France

Location

Institut Curie

Paris, France

Location

I.C.O. Gauducheau

Saint-Herblain, France

Location

Centre Paul Strauss - ICANS - Institut de cancérologie Strasbourg Europe

Strasbourg, France

Location

Institut Claudius Regaud - IUCT - Oncopole

Toulouse, France

Location

Institut Gustave Roussy

Villejuif, France

Location

ICO Badalona - Hospital Germans Trias i Pujol

Badalona, Spain

Location

Hospital Virgen de las Nieves

Granada, Spain

Location

Fundación de Investigación biomédica H. 12 de Octubre

Madrid, Spain

Location

Fundación de Investigación Biomédica Hospital Clínico San Carlos

Madrid, Spain

Location

Hospital Virgen de La Victoria

Málaga, Spain

Location

Hospital General de Valencia

Valencia, Spain

Location

Related Publications (1)

• 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 RESULT

MeSH Terms

Conditions

Neoplasms

Interventions

TG4001 vaccine; avelumab

Results Point of Contact

• Title: Director of Medical Affairs
• Organization: Transgene

clinical.trials@transgene.fr

+ 33 3 88 27 91 00

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2017
• First Posted: August 24, 2017
• Study Start: September 1, 2017
• Primary Completion: September 18, 2024
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 5, 2026
• Results First Posted: December 2, 2025

Record last verified: 2026-01

Locations

US (2); FR (12); ES (6)