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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03260023
Recruitment Status : Recruiting
First Posted : August 24, 2017
Last Update Posted : October 16, 2019
Merck KGaA, Darmstadt, Germany
EMD Serono Research & Development Institute, Inc.
Information provided by (Responsible Party):

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Head and Neck Squamous Cell Carcinoma HPV Positive Oropharyngeal Squamous Cell Carcinoma HPV-Related Carcinoma Biological: TG4001 Drug: Avelumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 52 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib/II Trial Evaluating the Combination of TG4001 and Avelumab in Patients With HPV-16 Positive Recurrent or Metastatic Malignancies Including Oropharyngeal Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Actual Study Start Date : September 11, 2017
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Avelumab

Arm Intervention/treatment
Experimental: TG4001/Avelumab Biological: TG4001
PhIb Dose escalation PhII established RP2D of the combination

Drug: Avelumab
Anti PD-L1

Primary Outcome Measures :
  1. 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:

    • 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

  2. Phase II: To evaluate the efficacy of TG4001 combined to avelumab in terms of Overall Response Rate (ORR) by using RECIST 1.1 in patients with recurrent or metastatic (R/M) HPV-16 positive advanced malignancies including oropharyngeal SCCHN. [ Time Frame: Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years ]

Secondary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years ]
    Using RECIST 1.1 (phase Ib part)

  2. Progression Free Survival (PFS) [ Time Frame: Every 6 weeks for the first 9 months, then every 12 weeks up to 3 years ]
    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.

  3. Overall Survival (OS) [ Time Frame: Every 3 months and up to 3 years ]
    Time from the date of first study treatment administration to the date of death due to any cause.

  4. 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.

  5. 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.

  6. Incidence of Adverse Event reported per CTCAE v4.03 [ Time Frame: up to 90 days after last study treatment administration ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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, anal, and oropharyngeal squamous cell carcinoma of head and neck.
  • 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%)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03260023

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Contact: Transgene EU, Clinical Operations Department + 33 (0) 3 88 27 91 00

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Angers Recruiting
Angers, France
Colmar Recruiting
Colmar, France
Lyon Recruiting
Lyon, France
Marseille Recruiting
Marseille, France
Nantes Recruiting
Nantes, France
Paris Recruiting
Paris, France
Strasbourg Recruiting
Strasbourg, France
Toulouse Recruiting
Toulouse, France
Granada Recruiting
Granada, Spain
Madrid Recruiting
Madrid, Spain
Malaga Recruiting
Malaga, Spain
Valencia Recruiting
Valencia, Spain
Sponsors and Collaborators
Merck KGaA, Darmstadt, Germany
EMD Serono Research & Development Institute, Inc.
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Responsible Party: Transgene Identifier: NCT03260023    
Other Study ID Numbers: TG4001.12
First Posted: August 24, 2017    Key Record Dates
Last Update Posted: October 16, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Transgene:
Anti PD-L1
Therapeutic Vaccine
Additional relevant MeSH terms:
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Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site