Combination Study With Eftilagimod Alpha (a Soluble LAG-3 Fusion Protein) and Pembrolizumab in Patients With Recurrent or Metastatic HNSCC

HNSCC Clinical Trial

— TACTI-003  

Official title:

TACTI-003 (Two ACTive Immunotherapeutics): A Multicenter, Open Label, Randomized, Phase II Trial to Investigate a Soluble LAG-3 Fusion Protein, Eftilagimod Alpha (Efti; IMP321) in Combination With Pembrolizumab (PD-1 Antagonist) for First Line Treatment of Subjects With Unresectable Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (HNSCC)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04811027
• Other study ID #: TACTI-003
• Secondary ID: Keynote- PNC-34
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 27, 2021
• Est. completion date: March 2025

Study information

• Verified date: November 2023
• Source: Immutep S.A.S.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Evaluate the safety and efficacy of eftilagimod alpha in combination with pembrolizumab against pembrolizumab alone in 1st line metastatic or recurrent HNSCC with PD-L1 positive (CPS ≥1) tumors, and determine the efficacy and safety of efti plus pembrolizumab in patients with PD-L1 negative tumors.

Description:

Up to 154 patients will be recruited in the TACTI-003 (Two ACTive Immunotherapies) Phase IIb study which will take place across several countries in Australia, Europe and United States of America in up to 35 experienced clinical sites. It will evaluate the safety and efficacy of eftilagimod alpha in combination with pembrolizumab against pembrolizumab alone in 1st line metastatic or recurrent HNSCC with PD-L1 positive (CPS ≥1) tumors, and determine the efficacy and safety of efti plus pembrolizumab in patients with PD-L1 negative tumors. Subjects in cohort A (CPS ≥1) will be randomized 1:1 to receive either "P+E": efti plus pembrolizumab or "P only": pembrolizumab alone. Subjects in cohort B (CPS <1) will receive a combination of efti and pembrolizumab "P+E". Efti will be administered for up to 24 months using a 30 mg s.c. dosing every 2 or 3 weeks. Pembrolizumab will be administered for up to 24 months using a 400mg i.v. (30 min) dosing every 6 weeks.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 171
• Est. completion date: March 2025
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Main Inclusion Criteria:

1. Histologically- or cytologically-confirmed recurrent disease not amenable to curative treatment with local or systemic therapy, or metastatic (disseminated) HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx that is considered incurable by local therapies and to be treated in the first line palliative setting and who are PD-X naïve.

2. Availability of tissue for PD-L1 biomarker analysis from a core or excisional biopsy.

3. Availability of PD-L1 biomarker result by using the FDA approved Dako standardized diagnostic test (PD-L1 IHC 22C3 pharmDx).

4. Availability of tissue for testing of human papillomavirus (HPV) status for oropharyngeal cancer (p16 expression testing).

5. ECOG performance status 0-1.

Main Exclusion Criteria:

1. Disease is suitable for local therapy administered with curative intent.

2. Previously treated with = 1 systemic regimen for recurrent and/or metastatic disease (with the exception of systemic therapy completed >6 months prior if given as part of multimodal treatment for locally or locoregionally advanced disease).

3. Histologically or cytologically confirmed head and neck cancer of any other primary anatomic location in the head and neck not specified in the inclusion criteria including subjects with HNSCC of unknown primary, squamous cell carcinoma originating from skin, or non-squamous histologies (e.g. nasopharynx, salivary gland or mucosal melanoma).

4. Has progressive disease (PD) within 6 months of completion of curatively intended systemic treatment for locally or locoregionally advanced HNSCC, or requires chemotherapy based therapeutic regimen due to e.g., rapidly progressing disease or need of aggressive sympton control.

5. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).

6. Has received prior chemotherapy, anti-cancer monoclonal antibody, major surgery, another systemic cancer therapy or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to cycle 1 day 1.

7. Known active central nervous system metastasis and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable: i.e. without evidence of progression documented by repeat imaging performed after therapy completed for CNS metastasis and with at least 4 weeks difference, clinically stable and without requirement for steroid treatment for at least 14 days prior to cycle 1 day 1.

8. Receives continuous systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 7 days prior to cycle 1 day 1. Inhaled or topical steroids and physiological replacement doses of up to 10 mg daily prednisone equivalents are permitted in the absence of active auto-immune disease.

Related Conditions & MeSH terms

• HNSCC
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• Eftilagimod alpha
APC activator, MHC II agonist, LAG-3 fusion protein
• Pembrolizumab
anti-PD-1 antibody

Locations

Country	Name	City	State
Australia	Macquarie University Hospital	Macquarie Park	New South Wales
Belgium	AZ Sint-Jan Brugge	Brugge
Belgium	Antwerp University Hospital	Edegem
Belgium	Centre Hospitalier Universitaire (CHU) de Liege	Liège
Belgium	AZ Nikolaas	Sint-Niklaas
Denmark	Rigshospitalet	Copenhagen
Denmark	Herlev Hospital	Herlev
Denmark	Odense University Hospital	Odense
Germany	Universitätsklinikum Bonn	Bonn	NRW
Germany	University Hospital Essen	Essen
Germany	Nationales Centrum für Tumorerkrankungen Heidelberg	Heidelberg
Germany	Universitätsklinikum Ulm	Ulm
Romania	The Oncology Institute "Prof Dr Ion Chiricuta" I.O.C.N.	Cluj-Napoca
Spain	Hospital de la Santa Creu i de Sant Pau	Barcelona
Spain	Vall d'Hebron Institute of Oncology (VHIO)	Barcelona
Spain	Institut Català d'Oncologia - Hospital Universitari de Girona	Girona
Spain	Hospital Universitario Lucus Augusti	Lugo
Spain	Hospital 12 Octubre	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	START Madrid (Hospital Universitario Fundación Jiménez Díaz)	Madrid
Spain	Hospital Universitario Miguel Servet	Zaragoza
Ukraine	Arensia Exploratory Medicine Llc	Kapitanivka	AL
United Kingdom	Institute of Cancer Science - Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	University College London Hospitals NHS Foundation - The Harley Street Clinic	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Nottingham University Hospitals, NHS Trust	Nottingham
United States	University of Alabama at Birmingham (UAB) - O'Neal Cancer Center	Birmingham	Alabama
United States	Oncology Consultants	Houston	Texas
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Immutep S.A.S.	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Denmark,  Germany,  Romania,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	PD-L1 expression		At Screening: three weeks prior to cycle 1 day 1
Other	Circulating level of TH1 biomarker		Up to 24 months
Other	Correlation of biomarkers or other characteristics with any efficacy or safety endpoint		Up to 24 months
Primary	Objective response rate (ORR) according to RECIST1.1		Up to 24 months
Secondary	Overall survival (OS)		Up to 24 months
Secondary	Objective response rate (ORR) according to iRECIST		Up to 24 months
Secondary	Time to and duration of responses according to iRECIST and RECIST 1.1		Up to 24 months
Secondary	Disease control rate according to iRECIST and RECIST 1.1		Up to 24 months
Secondary	Progression free survival (PFS) according to iRECIST and RECIST 1.1		Up to 24 months
Secondary	Occurrence of anti-efti-specific antibodies		Up to 24 months
Secondary	Frequency of (serious) adverse events		Up to 24 months
Secondary	Severity of (serious) adverse events		Up to 24 months
Secondary	Duration of (serious) adverse events		Up to 24 months
Secondary	Quality of Life using EORTC QLQ-H&N35		Up to 24 months