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

NCT03625323 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: TACTI-002Keynote-MK-3475-7982018-001994-25
• Study Type: interventional
• Target: 187
• Locations: 1 country
• Sites: 1

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.

Conditions

NSCLC; HNSCC

Outcome Measures

Primary Outcomes (2)

• Evaluation of Objective Response Rate (ORR) According to iRECIST (Unconfirmed)

  ORR was defined as the percentage of participants for each dose level whose best overall response is rated as iCR or iPR per immune Response Evaluation Criteria In Solid Tumors (iRECIST) for target lesions and assessed by CT or MRI. iCR was defined as disappearance of all target and non-target lesions and any pathological lymph nodes must be \<10 mm in the short axis. iPR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.

  Data collected from screening until time of disease progression, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 68 months

• Evaluation of Objective Response Rate (ORR) According to iRECIST (Confirmed)

  ORR was defined as the percentage of participants for each dose level whose best overall response is rated as iCR or iPR per immune Response Evaluation Criteria In Solid Tumors (iRECIST) for target lesions and assessed by CT or MRI. iCR was defined as disappearance of all target and non-target lesions and any pathological lymph nodes must be \<10 mm in the short axis. iPR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.

  Data collected from screening until time of disease progression, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 68 months

Secondary Outcomes (11)

• Duration of (Serious) Adverse Events

  up to 27 months

• Frequency of (Serious) Adverse Events

  up to 27 months

• Severity of (Serious) Adverse Events

  up to 27 months

• Time to Responses According to iRECIST and RECIST 1.1

  up to 68 months

• Duration of Responses According to iRECIST and RECIST 1.1

  up to 68 months

Study Arms (3)

1st line NSCLC

EXPERIMENTAL

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.

Drug: eftilagimod alpha; Drug: pembrolizumab (KEYTRUDA®)

2nd line NSCLC

EXPERIMENTAL

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.

Drug: eftilagimod alpha; Drug: pembrolizumab (KEYTRUDA®)

HNSCC

EXPERIMENTAL

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.

Drug: eftilagimod alpha; Drug: pembrolizumab (KEYTRUDA®)

Interventions

eftilagimod alpha DRUG

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

Also known as: IMP321, efti, eftilagimod alfa

1st line NSCLC; 2nd line NSCLC; HNSCC

pembrolizumab (KEYTRUDA®) DRUG

anti-PD-1 antibody

Also known as: MK-3475

1st line NSCLC; 2nd line NSCLC; HNSCC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.
• 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)
• 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)
• 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.

Sponsors & Collaborators

• Immutep S.A.S.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Oncology Consultants

Huston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 39403626 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

soluble LAG-3 protein, human; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Results Point of Contact

• Title: Immutep CMO
• Organization: Immutep

regulatoryaffairs@immutep.com

+ 49 30 88716843

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2018
• First Posted: August 10, 2018
• Study Start: February 21, 2019
• Primary Completion: June 2, 2022
• Study Completion: November 25, 2024
• Last Updated: April 22, 2026
• Results First Posted: December 18, 2024

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)