Clinical Trials /

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

Description:

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.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: TACTI-002
  • SECONDARY ID: Keynote-PN798
  • NCT ID: NCT03625323

Conditions

  • NSCLC
  • HNSCC

Interventions

DrugSynonymsArms
Eftilagimod alphaIMP321, Efti1st line NSCLC
PembrolizumabKeytruda, MK-34751st line NSCLC

Purpose

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 120 patients will be recruited in the TACTI-002 (Two ACTive Immunotherapies) Phase II
      study which will take place across approximately 15 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.
    

Trial Arms

NameTypeDescriptionInterventions
1st line NSCLCExperimentalEftilagimod 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.
  • Eftilagimod alpha
  • Pembrolizumab
2nd line NSCLCExperimentalEftilagimod 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.
  • Eftilagimod alpha
  • Pembrolizumab
HNSCCExperimentalEftilagimod 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.
  • Eftilagimod alpha
  • Pembrolizumab

Eligibility Criteria

        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).

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

               -  Symptomatic ascites or pleural effusion.

               -  > 1 line of chemotherapy for metastatic disease.

             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 for at least 4 weeks by
             repeat imaging, 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Evaluation of objective response rate (ORR) according to iRECIST
Time Frame:up to 24 month
Safety Issue:
Description:

Secondary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Immutep S.A.

Last Updated