A study of TG4001 and avelumab cancer immunotherapies in advanced HPV-induced malignancies

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Transgene

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

29 Aug 2017 → ongoing

Decision date (initial)

2024-07-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-515119-23-00

EudraCT number

2016-002799-28

ClinicalTrials.gov

NCT03260023

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Phase Ib objective: To evaluate the safety and tolerability of the combination of TG4001 plus avelumab in patients with recurrent or metastatic HPV-16 positive advanced malignancies.
Phase II part 1 objective: 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 squamous cell carcinoma of head and neck.
Phase II part 2 objective: To compare the Progression-Free Survival (PFS) of TG4001 in combination with avelumab vs avelumab alone in patients with recurrent or metastatic (R/M) HPV-16 positive advanced malignancies and without liver metastases at baseline.

Secondary objectives 7

1. To evaluate the combination of TG4001 and avelumab with respect to Overall response rate (ORR) by using RECIST 1.1 (phase Ib part and phase II part 2)
2. To evaluate the combination of TG4001 and avelumab with respect to Progression Free Survival (PFS, phase Ib and phase II part 1)
3. To evaluate the combination of TG4001 and avelumab with respect to Overall Survival (OS)
4. To evaluate the combination of TG4001 and avelumab with respect to Duration of Response (DoR)
5. To evaluate the combination of TG4001 and avelumab with respect to Disease control rate (DCR)
6. To evaluate the combination of TG4001 and avelumab with respect to safety profile (phase II part)
7. To evaluate the combination of TG4001 and avelumab with respect to percentage of patients with liver metastases at baseline who have disease progression at D43 (phase II part 2)

Conditions and MedDRA coding

Phase Ib and Phase II part 1: HPV-16 positive recurrent or metastatic malignancies including oropharyngeal squamous cell carcinoma of head and neck, cervical cancer, vulvar cancer, vaginal cancer, penile cancer, anal cancer Phase II part 2: HPV-16 positive recurrent or metastatic malignancies including cervical cancer, vulvar cancer, vaginal cancer, penile cancer, anal cancer

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Female or male patients, aged at least 18 years (no upper limit of age)
2. ECOG PS 0 or 1
3. Life expectancy of at least 3 months
4. Phase Ib and Phase II part 1: Patients with histologically or cytologically documented metastatic or refractory/recurrent HPV-16 + cancer (cervical, vulvar, vaginal, penile, anal cancers and oropharyngeal squamous cell carcinoma of head and neck); Phase II part 2: Patients with HPV-16+ cancers including cervical, vulvar, vaginal, penile, and anal cancer
5. Disease MUST not be amenable to curative surgery resection or curative radiotherapy with documented disease progression
6. Prior therapy: Phase Ib and Phase II part 1: 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 chemoradiation 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. Phase II part 2: - No more than one prior systemic treatment for recurrent /metastatic disease - Prior treatment for recurrent or metastatic disease is not required for: o Patients with recurrence/progression within 6 months after completion of prior multimodal therapy for localized or locally advanced disease o Patients who are unsuitable for platinum-based therapy o Patients who refuse chemotherapy or other standard therapies for the treatment of metastatic or recurrent disease
7. For patients with hepatic metastases - no more than 3 hepatic lesions in total (target and non-target lesions) - maximum size of hepatic target disease ≤ 30 mm according to RECIST 1.1
8. At least one measurable lesion by CT scan according to RECIST 1.1.
9. Adequate hematological, hepatic and renal function
10. Negative blood pregnancy test at screening for women of childbearing potential
11. 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 14

1. Prior exposure to cancer immunotherapy including cancer vaccines, any antibody/drug targeting T cell co-regulatory proteins (immune checkpoints)
2. 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
3. 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
4. Other active malignancy requiring concurrent systemic intervention
5. 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
6. Patient with any organ transplantation, including allogeneic stem cell transplantation
7. Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI-CTC V4.03), any history of anaphylaxis, or uncontrolled asthma
8. Any known allergy or reaction to eggs, gentamycin or attributed to compounds of similar chemical or biological composition to therapeutic vaccines/immunotherapeutic products
9. Any known allergy or reaction to any component of anti-PD-L1/PD-1 or its excipients
10. Patients with history of interstitial lung disease
11. 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
12. Significant chronic or acute infections including SARS-CoV-2 (COVID19) PCR positive testing
13. 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
14. 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%)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Phase Ib: safety and tolerability
2. Phase II part 1: overall response rate according to RECIST 1.1
3. Phase II part 2: progression-free survival according to RECIST 1.1

Secondary endpoints 7

1. Phase Ib: Overall response rate by using RECIST 1.1 and overall safety profile
2. Phase Ib and phase II part 2: Overall response rate by using RECIST 1.1
3. Phase Ib and phase II part 1: Progression Free Survival (PFS)
4. Overall Survival (OS)
5. Duration of Response (DoR)
6. Overall safety profile
7. Percentage of patients with liver metastases at baseline who have disease progression at D43 (phase II part 2)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Transgene

Sponsor organisation

Transgene

Address

Parc D Innovation, 400 Boulevard Gonthier D Andernach, Cs 80166 Illkirch Graffenstaden, Illkirch Graffenstaden 400 Boulevard Gonthier D Andernach Cs 80166 Illkirch Graffenstaden

City

Illkirch Cedex

Postcode

67405

Country

France

Scientific contact point

Organisation

Transgene

Contact name

Transgene Medical Affairs

Public contact point

Organisation

Transgene

Contact name

Transgene Medical Affairs

Third parties 11

Locations

2 EU/EEA countries · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications