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.
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
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
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
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
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