- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03260023
Phase Ib/II of TG4001 and Avelumab in HPV16 Positive R/M Cancers
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 patients at increasing doses of TG4001 in combination with avelumab according to a 3+3 design. There will be no intra-patient 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 patients 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 patients with HPV-16 positive advanced malignancies.
In both phases, tumor response will be evaluated on local assessment using RECIST 1.1.
All patients will be followed up until disease progression, death, or unacceptable toxicity, or study withdrawal for any reason, whichever occurs first.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Transgene EU, Clinical Operations Department
- Phone Number: + 33 (0) 3 88 27 91 00
- Email: clinical.trials@transgene.fr
Study Locations
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Angers, France
- I.C.O. Paul Papin
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Besançon, France
- CHU Besançon
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Bordeaux, France
- Hopital Saint Andre - CHU de Bordeaux
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Colmar, France
- Hôpitaux Civils de Colmar - Hôpital Pasteur
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Dijon, France
- CLCC Georges-François Leclerc
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Lyon, France
- Centre LEON BERARD
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Marseille, France
- Hopital de la Timone
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Paris, France
- Institut Curie
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Saint-Herblain, France
- I.C.O. Gauducheau
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Strasbourg, France
- Centre Paul Strauss - ICANS - Institut de cancérologie Strasbourg Europe
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Toulouse, France
- Institut Claudius Regaud - IUCT - Oncopole
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Villejuif, France
- Institut Gustave Roussy
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Badalona, Spain
- Ico Badalona - Hospital Germans Trias I Pujol
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Granada, Spain
- Hospital Virgen de las Nieves
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Madrid, Spain
- Fundación de Investigación biomédica H. 12 de Octubre
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Madrid, Spain
- Fundación de Investigación Biomédica Hospital Clínico San Carlos
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Malaga, Spain
- Hospital Virgen de la Victoria
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Valencia, Spain
- Hospital General de Valencia
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Florida
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Jacksonville, Florida, United States, 32224
- Mayo Clinic
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Female or male patients, aged at least 18 years (no upper limit of age)
- ECOG PS 0 or 1
- Life expectancy of at least 3 months
- Patients 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:
- Patients with recurrence/progression within 6 months after completion of prior multimodal therapy for localized or locally advanced disease
- Patients who are unsuitable for platinum-based therapy
- Patients who refuse chemotherapy or other standard therapies for the treatment of metastatic or recurrent disease
- Limited hepatic disease for patients 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 patients 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)
- Patients 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 patients 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
- Patients 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
- Patients 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
- Patient 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
- Patients with known history or any evidence of active interstitial lung disease / pneumonitis
- Patients 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: TG4001/Avelumab
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PhIb: Dose escalation PhII: Established RP2D for TG4001
Anti PD-L1
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Experimental: Avelumab
Applicable for Phase II part 2.
|
Anti PD-L1
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase Ib: To evaluate the safety and tolerability of the combination of TG4001 plus avelumab in patients with recurrent or metastatic HPV-16 positive advanced malignancies
Time Frame: Day 28
|
Dose limiting toxicities (DLTs) includes the following:
|
Day 28
|
Phase II part 1: Overall Response Rate (ORR) by RECIST 1.1
Time Frame: Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years
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Percentage of patients whose best overall response is either a Complete Response or a Partial Response according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria over the the total number of evaluable patients.
|
Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years
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Phase II part 2: Progression Free Survival (PFS) by RECISIT 1.1
Time Frame: Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years
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Time from the date of randomization to death due to any cause, whichever occurs first.
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Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Response Rate (ORR) by using RECIST 1.1 (phase Ib, phase II part 2)
Time Frame: Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years
|
Percentage of patients whose best overall response is either a Complete Response or a Partial Response according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria over the the total number of evaluable patients
|
Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years
|
Progression Free Survival (PFS) (phase Ib, Phase II part 1)
Time Frame: Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years
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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.
|
Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years
|
Overall Survival (OS)
Time Frame: Every 3 months and up to 3 years
|
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) to the date of death due to any cause.
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Every 3 months and up to 3 years
|
Duration of overall Response (DoR)
Time Frame: Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years
|
Time from first documented response (CR or PR) until documented disease progression or death, whichever occurs first.
|
Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years
|
Disease control rate (DCR)
Time Frame: Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years
|
Proportion of patients whose best overall response is either CR, PR, or SD.
|
Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years
|
Incidence of Adverse Event reported per CTCAE v4.03
Time Frame: up to 90 days after last study treatment administration
|
up to 90 days after last study treatment administration
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- TG4001.12
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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