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

NCT ID: NCT03625323

Last Updated: 2024-12-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 187 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-18
• Study Completion Date: 2024-11-25

Brief Summary

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.

Detailed Description

Up to 187 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.

Conditions

NSCLC; HNSCC

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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 (KEYTRUDA®): 200 mg every 3 weeks.

Group Type: EXPERIMENTAL

eftilagimod alpha

Intervention Type: DRUG

APC activator, MHC II agonist, LAG-3 fusion protein

pembrolizumab (KEYTRUDA®)

Intervention Type: DRUG

anti-PD-1 antibody

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 (KEYTRUDA®): 200 mg every 3 weeks.

Group Type: EXPERIMENTAL

eftilagimod alpha

Intervention Type: DRUG

APC activator, MHC II agonist, LAG-3 fusion protein

pembrolizumab (KEYTRUDA®)

Intervention Type: DRUG

anti-PD-1 antibody

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 (KEYTRUDA®): 200 mg every 3 weeks.

Group Type: EXPERIMENTAL

eftilagimod alpha

Intervention Type: DRUG

APC activator, MHC II agonist, LAG-3 fusion protein

pembrolizumab (KEYTRUDA®)

Intervention Type: DRUG

anti-PD-1 antibody

Interventions

eftilagimod alpha

APC activator, MHC II agonist, LAG-3 fusion protein

Intervention Type: DRUG

pembrolizumab (KEYTRUDA®)

anti-PD-1 antibody

Intervention Type: DRUG

Other Intervention Names

IMP321; efti; eftilagimod alfa; MK-3475

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Immutep S.A.S.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Oncology Consultants

Houston, Texas, United States

Countries

Australia; Poland; Spain; Ukraine; United Kingdom; United States

References

Krebs MG, Forster M, Majem M, Peguero J, Iams W, Clay T, Roxburgh P, Doger B, Bajaj P, Barba A, Perera S, Mueller C, Triebel F. Eftilagimod Alpha (a Soluble LAG-3 Protein) Combined With Pembrolizumab in Second-Line Metastatic NSCLC Refractory to Anti-Programmed Cell Death Protein 1/Programmed Death-Ligand 1-Based Therapy: Final Results from a Phase 2 Study. JTO Clin Res Rep. 2024 Aug 30;5(11):100725. doi: 10.1016/j.jtocrr.2024.100725. eCollection 2024 Nov.

Reference Type: DERIVED

PMID: 39403626 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Keynote-MK-3475-798

Identifier Type: OTHER

Identifier Source: secondary_id

2018-001994-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TACTI-002

Identifier Type: -

Identifier Source: org_study_id