Abstract 1033P
Background
Strata (St) A / B of the INSIGHT study evaluate feasibility of intratumoral (i.t.) and intraperitoneal (i.p.) IMP321 monotherapy in advanced solid tumors. The MHC class II agonist activates antigen presenting cells followed by CD8 T cell activation.
Methods
This is an investigator-initiated study with currently 4 St: i.t. (A) or i.p. IMP321 (B); s.c. IMP321 with SOC (C) or combined with avelumab (D). Here we focused on St A / B. In St A, patients (pts) received i.t. injections (inj) with IMP321 escalation 6-12-24-30mg in cohort (coh) 1 and the max. tolerated dose (MTD) in coh 2. In St B, pts with peritoneal carcinomatosis received i.p. IMP321 (dose escalation 1-3-6-12-30mg in coh 1 and MTD in coh 2). In both St pts with a benefit after the last inj. were offered s.c. IMP321 for up to 52 weeks. Main endpoint was safety.
Results
Recruitment has been completed with 8 pts treated in St A (coh 1: 3 pts. [2 gastric cancer, 1 peritoneal mesothelioma]; coh 2: 5 pts [cancer of head & neck, colon {2}, papilla, lung]) and 4 pts in St B coh 1 (2 gastric, 2 colon cancer). No dose limiting toxicities occurred. 14 serious adverse events (SAEs) have been reported: 8 in St A (2 in 1 pt of coh 1, 6 in 4 pts of coh 2) and 6 in 3 pts of St B coh 1. 1 SAE in coh 2 of St A was related to study procedure (sudden death NOS grade 5). 1 AESI (St A coh 1) probably related to IMP321 (chills grade 3). Of the heavily pretreated pts, 5 had stable disease (SD) (3 gastric, 2 colon cancer), 5 progressive disease (RECIST) and 2 clinical progression. 2 of the SD pts. had PFS of 3mo (1 gastric St A; 1 colon St B) and 2 SD pts. had PFS of 4mo (2 gastric St B). The SD gastric cancer pt of St A with PFS of 3 mo had an OS of 28 mo with increase of PD-L1 in the immune cells from 20% at baseline (BL) to 30% (D29 + D71). 3 SD pts with gastric cancer showed high CD45, CD163 expression at BL (tissue). Blood cytokine profile: 1 SD St B pt showed a significant increase in CXCL10, 4h - 24h after inj. measured on D1/D29, with similar peaks for IFN ɣ, combined with a moderate increase in CD4 and CD8 cells. Increase in IFN ɣ with additional Nk-cells was also seen in 1 SD St A pt.
Conclusions
Intratumoral and intraperitoneal IMP321 can be safely administered up to 30 mg with signals of clinical and cytokine activity.
Clinical trial identification
NCT03252938; EudraCT: 2016-002309-20.
Editorial acknowledgement
Legal entity responsible for the study
Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest.
Funding
Immutep GmbH.
Disclosure
S-E. Al-Batran: Research grant/Funding (self): Immutep. C. Brignone: Full/Part-time employment: Immutep. All other authors have declared no conflicts of interest.