Abstract 985P
Background
Stratum (Strat) D of the INSIGHT platform trial evaluates eftilagimod alpha (efti, IMP321) combined with avelumab in advanced solid tumors. The MHC class II agonist activates antigen-presenting cells followed by CD8 T-cell activation. Combination with PD-1/PD-L1 blockade aims at enhanced efficacy.
Methods
This trial consists of 5 strata: intratumoral (A) or intraperitoneal efti (B); s.c. efti with SOC (C) or with PD-L1 inhibition (D). Strat E is currently under development with a new efti combination. This abstract focuses on Strat D: 800mg avelumab i.v. q2w along with s.c. efti: 6 mg (coh 1, 6 pts), 30 mg (coh 2, 6 pts). Primary endpoint: safety.
Results
The trial was completed with 12 pts (coh 1: gastric, gallbladder, colon, pleural mesothelioma; coh 2: gastric, gastroesophageal, anal, rectum, cervix uteri). No dose limiting toxicities occurred. 10 serious adverse events were reported, none of them related (4 in 3 pts coh 1 [1 acute renal insufficiency grade 5 in 1 pt, 2 preileus grade 3 in 1 pt, 1 hearing impaired grade 4 in 1 pt] and 6 in 4 pts coh 2 [1 anal hemorrhage and 1 gallbladder obstruction in 1 pt, 1 eye pain and 1 feeding tube dislocation in 1 pt, each grade 3, 1 skin infection grade 2, 1 diffuse myocardial fibrosis grade 5]. 1 AE of special interest (AESI) possibly related with avelumab (sarcoidosis grade 1) occurred. 2 pts completed max treatment with 24 cycles. In coh 1 most common grade 1-2 AEs were nausea, pain; most common grade 3 AEs ileus, vomiting. 2 AEs grade 4 (hearing impaired, sepsis), 1 AE grade 5 (acute renal insufficiency) were reported. All AEs grade 3-5 were unrelated. In coh 2 most common grade 1-2 AE was hypothyroidism. 1 AE grade 5 (diffuse myocardial fibrosis) was reported. Only 1 AE grade 3 was related (urinary tract infection related with avelumab). 5 pts showed partial response, 1 stable disease, 5 progressive disease acc. to RECIST 1.1, 1 clinical progression. Activity was also observed in pre-treated non-immunogenic tumors. In the entire study population 75% are still alive, 66.7% of coh 1, 83.3% of coh 2.
Conclusions
Treatment with avelumab and efti is well tolerated, with promising signs of efficacy.
Clinical trial identification
EudraCT 2016-002309-20; NCT03252938.
Editorial acknowledgement
Legal entity responsible for the study
Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest.
Funding
Immutep GmbH and Pfizer, as part of an alliance between Merck KGaA, Darmstadt, Germany and Pfizer.
Disclosure
T.O. Goetze: Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: MSD Oncology; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Servier; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Servier; Financial Interests, Personal, Research Grant: Deutsche Forschungsgemeinschaft; Financial Interests, Personal, Research Grant: Deutsche Krebshilfe; Financial Interests, Personal, Research Grant: Gemeinsamer Bundesausschuss; Financial Interests, Personal, Research Grant: AstraZeneca. S. Al-Batran: Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Role: MacroGenics; Financial Interests, Personal, Advisory Role: Immutep; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: AIO gGmbH; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: MCI Group; Financial Interests, Personal, Ownership Interest: Institut für Klinische Krebsforschung GmbH; Financial Interests, Personal, Research Grant: Celgene; Financial Interests, Personal, Research Grant: Lilly; Financial Interests, Personal, Research Grant: Medac; Financial Interests, Personal, Research Grant: Hospira; Financial Interests, Personal, Research Grant: Sanofi; Financial Interests, Personal, Research Grant: German Cancer Aid; Financial Interests, Personal, Research Grant: German Research Foundation; Financial Interests, Personal, Research Grant: Federal Ministry of Education and Research; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Research Grant: Vifor Pharma; Financial Interests, Personal, Research Grant: Eurozyto; Financial Interests, Personal, Research Grant: Immutep; Financial Interests, Personal, Research Grant: Ipsen; Financial Interests, Personal, Research Grant: BMS; Financial Interests, Personal, Research Grant: Merck Sharp & Dohme; Financial Interests, Personal, Research Grant: AstraZeneca. All other authors have declared no conflicts of interest.