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

NSCLC Clinical Trial

— TACTI-002  

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03625323
• Other study ID #: TACTI-002
• Secondary ID: Keynote-PN798
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 18, 2019
• Est. completion date: November 2024

Study information

• Verified date: October 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 the combination of eftilagimod alpha with pembrolizumab in non-small cell lung carcinoma and head and neck carcinoma patients.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 189
• Est. completion date: November 2024
• Est. primary completion date: June 2, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HNSCC
• NSCLC
• 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	St John of God Subiaco Hospital	Perth
Australia	Tasman Health Care	Southport	Queensland
Spain	Consorci Corporació Sanitària Parc Taulí de Sabadell	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Institut Català d'Oncologia Badalona-Hospital Germans Trias i Pujol	Barcelona
Spain	Vall d' Hebron Institute of Oncology (VHIO) Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario Lucus Augusti	Lugo
Spain	Fundación Jiménez Díaz	Madrid
Spain	Hospital Universitario HM Sanchinarro	Madrid
Spain	Hospital Regional Universitario de Málaga	Málaga
Ukraine	Municipal Non-profit Enterprise "City Clinical Hospital #4" of Dnipro City Council	Dnipro
Ukraine	Medical and Diagnostic Centre of Private Enterprise of Private Manufacturing Company "Acinus"	Kropyvnytskyi
United Kingdom	The Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	University College London Hospitals NHS Foundation	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United States	Oncology Consultants	Houston	Texas
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (2)

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

Countries where clinical trial is conducted

United States,  Australia,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of objective response rate (ORR) according to iRECIST		up to 24 month
Secondary	Duration of (serious) adverse events		up to 24 month
Secondary	Frequency of (serious) adverse events		up to 24 month
Secondary	Severity of (serious) adverse events		up to 24 month
Secondary	Time to responses according to iRECIST and RECIST 1.1		up to 24 month
Secondary	Duration of responses according to iRECIST and RECIST 1.1		up to 24 month
Secondary	Response rate according to RECIST 1.1		up to 24 month
Secondary	Disease control rate according to iRECIST and RECIST 1.1		up to 24 month
Secondary	Progression free survival (PFS)		up to 42 month
Secondary	Overall survival (OS)		up to 42 month
Secondary	Occurrence of eftilagimod alpha-specific antibodies (ADA)		up to 24 month
Secondary	Plasma concentration time profile of eftilagimod alpha		up to 24 month