Combination Study With Soluble LAG-3 Fusion Protein Eftilagimod Alpha (IMP321) and Pembrolizumab in Patients With Previously Untreated Unresectable or Metastatic NSCLC, or Recurrent PD-X Refractory NSCLC or With Recurrent or Metastatic HNSCC (TACTI-002)

TACTI-002 (Two ACTive Immunotherapeutics): A Multicenter, Open Label, Phase II Study in Patients With Previously Untreated Unresectable or Metastatic Non-small Cell Lung Cancer (NSCLC), or Recurrent PD-X Refractory NSCLC or With Recurrent or Metastatic Squamous Head and Neck Cancer (HNSCC) Receiving the Soluble LAG-3 Fusion Protein Eftilagimod Alpha (IMP321) in Combination With Pembrolizumab (PD-1 Antagonist)

Evaluate the safety and efficacy of the combination of eftilagimod alpha with pembrolizumab in non-small cell lung carcinoma and head and neck carcinoma patients.

Study Overview

• Status: Active, not recruiting
• Conditions: NSCLC; HNSCC
• Intervention / Treatment: Drug: Eftilagimod alpha; Drug: Pembrolizumab

Detailed Description

Up to 189 patients will be recruited in the TACTI-002 (Two ACTive Immunotherapies) Phase II study which will take place across approximately 22 study centres in the U.S., Europe and Australia. It will evaluate the safety and efficacy of the combination of eftilagimod alpha with pembrolizumab in patients with advanced or metastatic non-small cell lung carcinoma or head and neck carcinoma. It will be a Simon's two-stage, non-comparative, open-label, single-arm, multicentre clinical study. Patients participating in the trial will be given the combination treatment for 12 months using a 30 mg s.c. eftilagimod alpha dosing every 2 or 3 weeks.

• Study Type: Interventional
• Enrollment (Actual): 189
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Perth, Australia, WA 6008
    • St John of God Subiaco Hospital
  • Queensland
    • Southport, Queensland, Australia, 4215
      • Tasman Health Care
• Spain
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08035
    • Vall d' Hebron Institute of Oncology (VHIO) Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08208
    • Consorci Corporació Sanitària Parc Taulí de Sabadell
  • Barcelona, Spain, 08916
    • Institut Català d'Oncologia Badalona-Hospital Germans Trias i Pujol
  • Lugo, Spain, 27003
    • Hospital Universitario Lucus Augusti
  • Madrid, Spain, 28040
    • Fundacion Jimenez Diaz
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro
  • Málaga, Spain, 29010
    • Hospital Regional Universitario de Málaga
• Ukraine
  • Dnipro, Ukraine, 49102
    • Municipal Non-profit Enterprise "City Clinical Hospital #4" of Dnipro City Council
  • Kropyvnytskyi, Ukraine, 25006
    • Medical and Diagnostic Centre of Private Enterprise of Private Manufacturing Company "Acinus"
• United Kingdom
  • Glasgow, United Kingdom
    • The Beatson West of Scotland Cancer Centre
  • London, United Kingdom, W1T 7HA
    • University College London Hospitals NHS Foundation
  • Manchester, United Kingdom, M20 4BX
    • The Christie Nhs Foundation Trust
• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Oncology Consultants

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Main Inclusion Criteria:

1. Part A (1st line, PD-X naïve NSCLC): histologically- or cytologically-confirmed diagnosis of non-small cell lung carcinoma stage IIIB not amenable to curative treatment or stage IV not amenable to EGFR/ALK based therapy, treatment naïve for systemic therapy given for advanced/metastatic disease (previous palliative radiotherapy for advanced/metastatic disease acceptable)

   Part B (2nd line, PD-X refractory NSCLC): histologically- or cytologically-confirmed diagnosis of NSCLC after failure of first-line treatment (for metastatic disease) with at least 2 cycles of any PD-1/PD-L1 containing based therapy (e.g. nivolumab, pembrolizumab, avelumab, durvalumab, etc.) alone, or in combination with any other immunotherapeutic or chemotherapy given as part of first-line treatment.

   Part C (2nd line PD-X naive HNSCC): 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, and larynx that is considered incurable by local therapies after failure of prior platinum-based therapy.

2. Submission of formalin-fixed diagnostic tumor tissue
3. ECOG performance status 0-1.
4. Expected survival > 3 months.

Main Exclusion Criteria:

1. For part A (1st line, PD-X naïve NSCLC):

   • The NSCLC can be treated with curative intent with either surgical resection and/or chemoradiation and/or radiation.
   • Has received systemic therapy for the treatment of their stage IV NSCLC. Completion of treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic disease.
   • EGFR-sensitizing mutation and/or is EML4 gene/ ALK gene fusion positive (ALK translocation).
   • Lung radiation therapy that is >30Gy within 6 months of the first dose of trial treatment.

   For Part B (2nd line, PD-X refractory NSCLC):

   • Symptomatic ascites or pleural effusion.
   • > 1 line of chemotherapy for metastatic disease.
   • Lung radiation therapy that is >30Gy within 6 months of the first dose of trial treatment.

   For Part C (2nd line PD-X naive HNSCC):

   • Disease is suitable for local therapy administered with curative intent.
   • Previously treated with > 1 systemic regimens for recurrent and/or metastatic disease.
2. 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) (Part A and C only)
3. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137) and was discontinued from that treatment due to a Grade 3 or higher irAE (Part B only)

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

   Note: Patients must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Patients with ≤Grade 2 neuropathy, alopecia and elevated transaminases in case of liver metastases may be eligible. If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.

5. Known active central nervous system metastasis and/or carcinomatous meningitis. Patients 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.
6. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1st line NSCLC; Eftilagimod alpha: 30 mg every 2 weeks for the first 8 cycles (1 cycle = 3 weeks) and every 3 weeks thereafter (starting cycle 9). Pembrolizumab: 200 mg every 3 weeks.	Drug: Eftilagimod alpha; APC activator, MHC II agonist, LAG-3 fusion protein; Other Names: IMP321; Efti; Drug: Pembrolizumab; anti-PD-1 antibody; Other Names: Keytruda; MK-3475
Experimental: 2nd line NSCLC; Eftilagimod alpha: 30 mg every 2 weeks for the first 8 cycles (1 cycle = 3 weeks) and every 3 weeks thereafter (starting cycle 9). Pembrolizumab: 200 mg every 3 weeks.	Drug: Eftilagimod alpha; APC activator, MHC II agonist, LAG-3 fusion protein; Other Names: IMP321; Efti; Drug: Pembrolizumab; anti-PD-1 antibody; Other Names: Keytruda; MK-3475
Experimental: HNSCC; Eftilagimod alpha: 30 mg every 2 weeks for the first 8 cycles (1 cycle = 3 weeks) and every 3 weeks thereafter (starting cycle 9). Pembrolizumab: 200 mg every 3 weeks.	Drug: Eftilagimod alpha; APC activator, MHC II agonist, LAG-3 fusion protein; Other Names: IMP321; Efti; Drug: Pembrolizumab; anti-PD-1 antibody; Other Names: Keytruda; MK-3475

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evaluation of objective response rate (ORR) according to iRECIST	up to 24 month

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of (serious) adverse events	up to 24 month
Frequency of (serious) adverse events	up to 24 month
Severity of (serious) adverse events	up to 24 month
Time to responses according to iRECIST and RECIST 1.1	up to 24 month
Duration of responses according to iRECIST and RECIST 1.1	up to 24 month
Response rate according to RECIST 1.1	up to 24 month
Disease control rate according to iRECIST and RECIST 1.1	up to 24 month
Progression free survival (PFS)	up to 42 month
Overall survival (OS)	up to 42 month
Occurrence of eftilagimod alpha-specific antibodies (ADA)	up to 24 month
Plasma concentration time profile of eftilagimod alpha	up to 24 month

Collaborators and Investigators

• Sponsor: Immutep S.A.S.
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2019
• Primary Completion (Actual): June 2, 2022
• Study Completion (Estimated): November 1, 2024

Study Registration Dates

• First Submitted: July 16, 2018
• First Submitted That Met QC Criteria: August 9, 2018
• First Posted (Actual): August 10, 2018

Study Record Updates

• Last Update Posted (Actual): October 24, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: TACTI-002; Keynote-PN798 (Other Identifier: Merck Sharp & Dohme Corp)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No