Clinical Trials /

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

NCT03260023

Description:

The study will consist of two parts : In the phase Ib part: 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, evaluation of efficacy and further evaluation of safety of the combination of TG4001 and avelumab will be performed. In both parts, tumor response will be evaluated on local assessment using RECIST 1.1. All patients will be followed up until disease progression or death due to any cause or the date of data cut-off, whichever occurs first.

Related Conditions:
  • Anal Squamous Cell Carcinoma
  • Cervical Squamous Cell Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
  • Penile Carcinoma
  • Vaginal Squamous Cell Carcinoma
  • Vulvar Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase Ib/II of TG4001 and Avelumab in HPV16 Positive R/M Cancers and Expansion Cohort to Oropharyngeal SCCHN
  • Official Title: A Phase Ib/II Trial Evaluating the Combination of TG4001 and Avelumab in Patients With HPV-16 Positive Recurrent or Metastatic Malignancies and Expansion Cohort to Oropharyngeal Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Clinical Trial IDs

  • ORG STUDY ID: TG4001.12
  • NCT ID: NCT03260023

Conditions

  • Head and Neck Squamous Cell Carcinoma
  • HPV Positive Oropharyngeal Squamous Cell Carcinoma
  • HPV-Related Carcinoma

Interventions

DrugSynonymsArms
TG4001TG4001/Avelumab
AvelumabTG4001/Avelumab

Purpose

The study will consist of two parts : In the phase Ib part: 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, evaluation of efficacy and further evaluation of safety of the combination of TG4001 and avelumab will be performed in a single arm cohort of patients with HPV-16 positive oropharyngeal SCCHN. In both parts, tumor response will be evaluated on local assessment using RECIST 1.1. All patients will be followed up until disease progression or death due to any cause or the date of data cut-off, whichever occurs first.

Trial Arms

NameTypeDescriptionInterventions
TG4001/AvelumabExperimental
  • Avelumab

Eligibility Criteria

        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. Phase Ib: cervical, vulvar, vaginal, penile,
             anal, and oropharyngeal squamous cell carcinoma of head and neck. Phase II part: an
             expansion cohort of oropharyngeal SCCHN will be included

          -  Disease MUST not be amenable to curative surgery resection or curative radiotherapy
             with documented disease progression

          -  Prior therapy: Patients MAY have received up to 2 prior lines of systemic chemotherapy
             for the management of metastatic or recurrent disease; for SCCHN, patients MUST have
             previously been exposed to platinum-based therapy, either as part of definitive
             chemo-radiation OR as first line systemic treatment for metastatic disease which may
             include cetuximab. Patients with recurrence/progression within 6 months of prior
             multimodal therapy using platinum-based therapy are eligible. Patients with cervical
             cancer may have undergone surgery and/or received definitive radiation or
             chemo-radiation therapy for localized disease.

          -  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
             V4.03), 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 history of interstitial lung disease

          -  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 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%)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
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

Secondary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years
Safety Issue:
Description:Using RECIST 1.1 (phase Ib part)
Measure:Progression Free Survival (PFS)
Time Frame:Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years
Safety Issue:
Description:Time from the date of first study treatment administration to the date of first documented tumor progression or death due to any cause, whichever occurs first.
Measure:Overall Survival (OS)
Time Frame:Every 3 months and up to 3 years
Safety Issue:
Description:Time from the date of first study treatment administration to the date of death due to any cause.
Measure:Duration of overall Response (DoR)
Time Frame:Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years
Safety Issue:
Description:Time from first documented response (CR or PR) until documented disease progression or death, whichever occurs first.
Measure:Disease control rate (DCR)
Time Frame:Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years
Safety Issue:
Description:Proportion of patients whose best overall response is either CR, PR, or SD.
Measure:Incidence of Adverse Event reported per CTCAE v4.03
Time Frame:up to 90 days after last study treatment administration
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Transgene

Trial Keywords

  • Avelumab
  • Cancer
  • Anti PD-L1
  • Therapeutic Vaccine

Last Updated

January 16, 2018