Trial Outcomes & Findings for 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 (NCT NCT03625323)

Last Updated: 2026-04-22

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

187 participants

Primary outcome timeframe

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

Results posted on

2026-04-22

Participant Flow

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).

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).

Participant milestones

Participant milestones
Measure	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	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	2nd Line 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
Overall Study STARTED	114	36	37
Overall Study COMPLETED	22	2	4
Overall Study NOT COMPLETED	92	34	33

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1st Line NSCLC n=114 Participants 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	2nd Line NSCLC n=36 Participants 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	HNSCC n=37 Participants 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	Total n=187 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=60 Participants	0 Participants n=56 Participants	0 Participants n=116 Participants	0 Participants n=7 Participants
Age, Categorical Between 18 and 65 years	39 Participants n=60 Participants	15 Participants n=56 Participants	20 Participants n=116 Participants	74 Participants n=7 Participants
Age, Categorical >=65 years	75 Participants n=60 Participants	21 Participants n=56 Participants	17 Participants n=116 Participants	113 Participants n=7 Participants
Age, Continuous	67 Years n=60 Participants	67 Years n=56 Participants	63 Years n=116 Participants	67 Years n=7 Participants
Sex: Female, Male Female	30 Participants n=60 Participants	14 Participants n=56 Participants	4 Participants n=116 Participants	48 Participants n=7 Participants
Sex: Female, Male Male	84 Participants n=60 Participants	22 Participants n=56 Participants	33 Participants n=116 Participants	139 Participants n=7 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=60 Participants	0 Participants n=56 Participants	0 Participants n=116 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Asian	1 Participants n=60 Participants	0 Participants n=56 Participants	1 Participants n=116 Participants	2 Participants n=7 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=60 Participants	0 Participants n=56 Participants	0 Participants n=116 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Black or African American	2 Participants n=60 Participants	2 Participants n=56 Participants	0 Participants n=116 Participants	4 Participants n=7 Participants
Race (NIH/OMB) White	109 Participants n=60 Participants	34 Participants n=56 Participants	35 Participants n=116 Participants	178 Participants n=7 Participants
Race (NIH/OMB) More than one race	0 Participants n=60 Participants	0 Participants n=56 Participants	0 Participants n=116 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=60 Participants	0 Participants n=56 Participants	1 Participants n=116 Participants	3 Participants n=7 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=60 Participants	4 Participants n=56 Participants	1 Participants n=116 Participants	10 Participants n=7 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	109 Participants n=60 Participants	32 Participants n=56 Participants	36 Participants n=116 Participants	177 Participants n=7 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=60 Participants	0 Participants n=56 Participants	0 Participants n=116 Participants	0 Participants n=7 Participants
Smoking history Non-smoker	6 Participants n=60 Participants	5 Participants n=56 Participants	5 Participants n=116 Participants	16 Participants n=7 Participants
Smoking history Ex- or current smoker	108 Participants n=60 Participants	31 Participants n=56 Participants	32 Participants n=116 Participants	171 Participants n=7 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	HNSCC n=37 Participants 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	1st Line NSCLC n=114 Participants 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	2nd Line NSCLC n=36 Participants 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
Evaluation of Objective Response Rate (ORR) According to iRECIST (Unconfirmed)	11 Participants	46 Participants	3 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	HNSCC n=37 Participants 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	1st Line NSCLC n=114 Participants 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	2nd Line NSCLC n=36 Participants 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
Evaluation of Objective Response Rate (ORR) According to iRECIST (Confirmed)	10 Participants	40 Participants	3 Participants

Outcome measures

Outcome data not reported

Adverse Events

1st Line NSCLC

Serious events: 54 serious events

Other events: 114 other events

Deaths: 84 deaths

2nd Line NSCLC

Serious events: 9 serious events

Other events: 35 other events

Deaths: 30 deaths

2nd Line HNSCC

Serious events: 20 serious events

Other events: 36 other events

Deaths: 31 deaths

Serious adverse events

Other adverse events

Additional Information

Immutep CMO

Immutep

Phone: + 49 30 88716843

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Approval from the Sponsor is required for the PI to publish or disseminate results from the medical investigation.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	1st Line NSCLC n=114 participants at risk 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	2nd Line NSCLC n=36 participants at risk 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	2nd Line HNSCC n=37 participants at risk 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
Respiratory, thoracic and mediastinal disorders Dyspnea	7.0% 8/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Respiratory, thoracic and mediastinal disorders Pneumonitis	3.5% 4/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.7% 1/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
General disorders Gait disturbance	0.88% 1/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
General disorders General physical health deterioration	0.88% 1/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Metabolism and nutrition disorders Dehydration	0.00% 0/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.7% 1/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.7% 1/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.8% 1/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.88% 1/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Investigations Aspartate aminotransferase increased	0.88% 1/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.00% 0/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.7% 1/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Investigations Biopsy lymph gland	0.88% 1/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Musculoskeletal and connective tissue disorders Neck pain	0.88% 1/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.7% 1/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.00% 0/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.7% 1/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Injury, poisoning and procedural complications Femur fracture	0.88% 1/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Injury, poisoning and procedural complications Gastrointestinal stoma complication	0.88% 1/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Injury, poisoning and procedural complications Procedural pain	0.88% 1/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.7% 1/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Injury, poisoning and procedural complications Toxicity to various agents	0.00% 0/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.7% 1/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Nervous system disorders Metabolic encephalopathy	0.00% 0/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.7% 1/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Nervous system disorders Peripheral sensory neuropathy	0.88% 1/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Vascular disorders Arterial thrombosis	0.88% 1/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Vascular disorders Hypertension	0.88% 1/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Vascular disorders Peripheral ischaemia	0.88% 1/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Infections and infestations Lower respiratory tract infection	1.8% 2/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.8% 1/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.7% 1/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Respiratory, thoracic and mediastinal disorders Hemoptysis	3.5% 4/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Infections and infestations Pneumonia	2.6% 3/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.8% 1/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.7% 1/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Hepatobiliary disorders Bile duct stone	0.88% 1/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	0.88% 1/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.8% 1/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.4% 2/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Cardiac disorders Atrial fibrillation	2.6% 3/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
General disorders Death (unknown cause)	2.6% 3/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Infections and infestations COVID-19	2.6% 3/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Infections and infestations COVID-19 pneumonia	1.8% 2/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Infections and infestations Urinary tract infection	0.00% 0/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.4% 2/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.4% 2/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Nervous system disorders Syncope	0.00% 0/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.4% 2/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Blood and lymphatic system disorders Anemia	2.6% 3/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.8% 1/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Cardiac disorders Cardiac failure	1.8% 2/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.88% 1/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.8% 1/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Gastrointestinal disorders Constipation	0.88% 1/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.8% 1/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality

Other adverse events
Measure	1st Line NSCLC n=114 participants at risk 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	2nd Line NSCLC n=36 participants at risk 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	2nd Line HNSCC n=37 participants at risk 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
Musculoskeletal and connective tissue disorders Musculoskeletal pain	11.4% 13/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	11.1% 4/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.4% 2/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Musculoskeletal and connective tissue disorders Pain in extremity	7.0% 8/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.8% 1/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.4% 2/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Musculoskeletal and connective tissue disorders Neck pain	7.0% 8/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.8% 1/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	8.1% 3/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
General disorders Chest pain	0.88% 1/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.6% 2/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
General disorders Facial pain	0.88% 1/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.4% 2/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
General disorders Pain	0.88% 1/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.4% 2/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
General disorders Face oedema	0.00% 0/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.4% 2/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Respiratory, thoracic and mediastinal disorders Dyspnoea	34.2% 39/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	36.1% 13/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	8.1% 3/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Respiratory, thoracic and mediastinal disorders Cough	29.8% 34/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	30.6% 11/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	18.9% 7/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Respiratory, thoracic and mediastinal disorders Haemoptysis	13.2% 15/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.8% 1/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.4% 2/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Respiratory, thoracic and mediastinal disorders Productive cough	10.5% 12/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	8.3% 3/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Respiratory, thoracic and mediastinal disorders Dysphonia	2.6% 3/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.6% 2/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.4% 2/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	1.8% 2/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.6% 2/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Respiratory, thoracic and mediastinal disorders Wheezing	0.88% 1/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.6% 2/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Gastrointestinal disorders Nausea	16.7% 19/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	16.7% 6/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	10.8% 4/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Gastrointestinal disorders Constipation	18.4% 21/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	11.1% 4/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.4% 2/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Gastrointestinal disorders Diarrhoea	17.5% 20/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	8.3% 3/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	13.5% 5/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Gastrointestinal disorders Vomiting	11.4% 13/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	13.9% 5/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	8.1% 3/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Gastrointestinal disorders Dysphagia	6.1% 7/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.8% 1/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.7% 1/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Gastrointestinal disorders Abdominal pain	5.3% 6/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	8.3% 3/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.4% 2/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Gastrointestinal disorders Abdominal pain upper	6.1% 7/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.6% 2/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Gastrointestinal disorders Stomatitis	1.8% 2/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.8% 1/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	10.8% 4/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Gastrointestinal disorders Dry mouth	5.3% 6/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Musculoskeletal and connective tissue disorders Arthralgia	16.7% 19/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	19.4% 7/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	10.8% 4/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Musculoskeletal and connective tissue disorders Back pain	13.2% 15/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	8.3% 3/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	13.5% 5/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Metabolism and nutrition disorders Dehydration	1.8% 2/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.8% 1/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.4% 2/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Metabolism and nutrition disorders Hypokalaemia	0.88% 1/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.8% 1/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.4% 2/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Metabolism and nutrition disorders Hypoalbuminaemia	0.88% 1/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.4% 2/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.4% 2/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Infections and infestations Pneumonia	7.0% 8/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.6% 2/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.4% 2/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Infections and infestations Upper respiratory tract infection	4.4% 5/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	8.3% 3/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	10.8% 4/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Infections and infestations Urinary tract infection	6.1% 7/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.8% 1/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	8.1% 3/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Infections and infestations COVID-19	7.0% 8/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.6% 2/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.7% 1/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Infections and infestations Bronchitis	3.5% 4/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.8% 1/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.4% 2/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Infections and infestations Oral candidiasis	3.5% 4/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.8% 1/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.4% 2/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Infections and infestations Respiratory tract infection	4.4% 5/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.8% 1/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.4% 2/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Infections and infestations Lower respiratory tract infection	2.6% 3/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.6% 2/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.7% 1/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Infections and infestations Rhinitis	2.6% 3/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	5.6% 2/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	0.00% 0/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Investigations Weight decreased	5.3% 6/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	16.7% 6/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	18.9% 7/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality
Investigations Amylase increased	11.4% 13/114 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	8.3% 3/36 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality	2.7% 1/37 • Up to 27 months Reported data is based on adverse events with onset dates on or after the first dose of study drug regardless of causality