HNSCC, NSCLC
Conditions
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.
Interventions
APC activator, MHC II agonist, LAG-3 fusion protein
DRUGpembrolizumab (KEYTRUDA®)
anti-PD-1 antibody
Sponsors
Immutep S.A.S.
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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). * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of Objective Response Rate (ORR) According to iRECIST (Unconfirmed) | 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 | 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. |
| Evaluation of Objective Response Rate (ORR) According to iRECIST (Confirmed) | 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 | 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. |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Response Rate According to RECIST 1.1 | up to 68 months |
| Disease Control Rate According to iRECIST and RECIST 1.1 | up to 68 months |
| Progression Free Survival (PFS) | up to 68 months |
| Overall Survival (OS) | up to 68 months |
| Occurrence of Eftilagimod Alpha-specific Antibodies (ADA) | up to 24 month |
| Plasma Concentration Time Profile of Eftilagimod Alpha | up to 24 month |
Countries
United States
Participant flow
Recruitment details
The first ICF for the study was signed on February 21, 2019. Recruitment ended on November 30, 2021. 18 sites in 6 countries. Number of sites per country: Australia (2), Poland (1), Spain (8), UK (3), Ukraine (2) and US (2).
Pre-assignment details
Participants could enrol in the study if: NSCLC previously untreated for stage IIIB or stage IV disease (Part A); NSCLC after confirmed progression on first-line treatment and proven resistance to PD (L)1 inhibitors (Part B) or HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx after failure of prior platinum-based therapy (Part C).
Participants by arm
| Arm | Count |
|---|---|
| 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: 200 mg every 3 weeks.
Eftilagimod alpha: APC activator, MHC II agonist, LAG-3 fusion protein
Pembrolizumab: anti-PD-1 antibody | 114 |
| 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: 200 mg every 3 weeks.
Eftilagimod alpha: APC activator, MHC II agonist, LAG-3 fusion protein
Pembrolizumab: anti-PD-1 antibody | 36 |
| 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: 200 mg every 3 weeks.
Eftilagimod alpha: APC activator, MHC II agonist, LAG-3 fusion protein
Pembrolizumab: anti-PD-1 antibody | 37 |
| Total | 187 |
Baseline characteristics
| Characteristic | 1st Line NSCLC | 2nd Line NSCLC | HNSCC | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 75 Participants | 21 Participants | 17 Participants | 113 Participants |
| Age, Categorical Between 18 and 65 years | 39 Participants | 15 Participants | 20 Participants | 74 Participants |
| Age, Continuous | 67 Years | 67 Years | 63 Years | 67 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 4 Participants | 1 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 109 Participants | 32 Participants | 36 Participants | 177 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 109 Participants | 34 Participants | 35 Participants | 178 Participants |
| Sex: Female, Male Female | 30 Participants | 14 Participants | 4 Participants | 48 Participants |
| Sex: Female, Male Male | 84 Participants | 22 Participants | 33 Participants | 139 Participants |
| Smoking history Ex- or current smoker | 108 Participants | 31 Participants | 32 Participants | 171 Participants |
| Smoking history Non-smoker | 6 Participants | 5 Participants | 5 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 84 / 114 | 30 / 36 | 31 / 37 |
| other Total, other adverse events | 114 / 114 | 35 / 36 | 36 / 37 |
| serious Total, serious adverse events | 54 / 114 | 9 / 36 | 20 / 37 |
Outcome results
Primary
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.
Time frame: 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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1st Line NSCLC | Evaluation of Objective Response Rate (ORR) According to iRECIST (Confirmed) | 40 Participants |
| 2nd Line NSCLC | Evaluation of Objective Response Rate (ORR) According to iRECIST (Confirmed) | 3 Participants |
| HNSCC | Evaluation of Objective Response Rate (ORR) According to iRECIST (Confirmed) | 10 Participants |
Primary
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.
Time frame: 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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1st Line NSCLC | Evaluation of Objective Response Rate (ORR) According to iRECIST (Unconfirmed) | 46 Participants |
| 2nd Line NSCLC | Evaluation of Objective Response Rate (ORR) According to iRECIST (Unconfirmed) | 3 Participants |
| HNSCC | Evaluation of Objective Response Rate (ORR) According to iRECIST (Unconfirmed) | 11 Participants |
Secondary
Disease Control Rate According to iRECIST and RECIST 1.1
Time frame: up to 68 months
Secondary
Duration of Responses According to iRECIST and RECIST 1.1
Time frame: up to 68 months
Secondary
Duration of (Serious) Adverse Events
Time frame: up to 27 months
Secondary
Frequency of (Serious) Adverse Events
Time frame: up to 27 months
Secondary
Occurrence of Eftilagimod Alpha-specific Antibodies (ADA)
Time frame: up to 24 month
Secondary
Overall Survival (OS)
Time frame: up to 68 months
Secondary
Plasma Concentration Time Profile of Eftilagimod Alpha
Time frame: up to 24 month
Secondary
Progression Free Survival (PFS)
Time frame: up to 68 months
Secondary
Response Rate According to RECIST 1.1
Time frame: up to 68 months
Secondary
Severity of (Serious) Adverse Events
Time frame: up to 27 months
Secondary
Time to Responses According to iRECIST and RECIST 1.1
Time frame: up to 68 months