IMMUTEP LIMITED #985P: Advanced safety and efficacy data from stratum D of the phase I INSIGHT platform
trial evaluating feasibility and safety of eftilagimod alpha combined with avelumab in
advanced solid tumors
Thorsten O. Goetze1,3, Daniel W. Mueller1,3, Mohammad-Reza Rafiyan2, Dragan Kiselicki2, Timursah Habibzade2, Marina Schaaf3, Regina Eickhoff3, Elke Jäger2, Salah-EddinAl-Batran1,3
1Krankenhaus Nordwest, University Cancer Center Frankfurt, Frankfurt, Germany; 2Krankenhaus Nordwest, Frankfurt, Germany;
3 Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest, Frankfurt, Germany
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: 6mg (cohort 1, 6 pts), 30mg (cohort 2, 6 pts). Primary endpoint is safety..
Table 3: Serious adverse events (irrespective of relationship to study drug)
Cohort 1 | Cohort 2 | Total | ||||||||
800mg avelumab + 6mg efti | 800mg avelumab + 30mg efti | |||||||||
n=6 (%) | n=6 (%) | n=12 (%) | ||||||||
Serious adverse event | G3 | G4 | G5 | G2 | G3 | G5 | G2 | G3 | G4 | G5 |
Acute renal insufficiency | 1 | (17%) | 1 | (8%) | ||||||
Ileus | 1 (17%) | 1 | (8%) | |||||||
Anal hemorrhage | 1 | (17%) | 1 | (8%) | ||||||
Diffuse myocardial fibrosis | 1 | (17%) | 1 | (8%) | ||||||
Gallbladder obstruction | 1 | (17%) | 1 | (8%) |
Figure 1: Study Design
Table 1: Patient overview
Pat-ID | Cohort | Indication | Last prior therapy | PD-L1 staining / MSI / | No of | No of | No of | Best | PFS | OS | ||
molecular markes | cycles | efti | avelumab | response | (months) | (months) | ||||||
injections | adminin. | |||||||||||
total | total | |||||||||||
001-017 | Cohort 1 | Adenocarcinoma | 1st line FLOT | PD-L1: nk; MSS | 5 | 5 | 5 | PD | 1.9 | 19.4 | ||
stomach | ||||||||||||
001-018 | Cohort 1 | Adenocarcinoma | Gemcitabine / cisplatin | PD-L1: CPS 80%, MSS | 3 | 3 | 3 | PD* | 1.7 | 1.7 | ||
gallbladder | additive | |||||||||||
001-019 | Cohort 1 | Adenocarcinoma | 3rd line TAS-102 | PD-L1: nk; Pan-RAS wt | 4 | 4 | 4 | PD | 1.8 | 6.1 | ||
right colon | ||||||||||||
001-020 | Cohort 1 | Adenocarcinoma | 3rd line TAS-102 | PD-L1: nk; Pan-RAS and | 4 | 4 | 4 | PD | 2.0 | 21.0 | ||
rectum | BRAF wt | |||||||||||
Adenocarcinoma | PD-L1: TPS 1%, CPS | |||||||||||
001-021** | Cohort 1 | na | 2%; MSI high (Lynch- | 24 | 12 | 24 | PR | 17.8 | 18.9 | |||
right colon | Syndrome) | |||||||||||
001-022 | Cohort 1 | Pleural | na | Nk | 16 | 12 | 16 | PR | 7.5 | 17.9 | ||
mesothelioma | ||||||||||||
Squamous cell | Def. RCTx carboplatin/ | |||||||||||
001-023 | Cohort 2 esophageal | PD-L1: CPS 30% | 3 | 3 | 3 | SD | 1.5 | 13.2 | ||||
carcinoma | paclitaxel (56 Gy) | |||||||||||
001-024 | Cohort 2 | Squamous cell anal | Def. RCTx (5-FU+ | PD-L1: TPS 50% | 24 | 12 | 24 | PR | 12.8 | 14.2 | ||
carcinoma | mitomoycin C) | |||||||||||
001-025 | Cohort 2 | Adenocarcinoma | 2nd line paclitaxel / | PD-L1: TPS 30%, | 17 | 12 | 17 | PR | 7.4 | 13.4 | ||
GEJ Typ III | ramucirumab | CPS 40% | ||||||||||
001-026** | Cohort 2 | Squamous cell | Def. RCTx (cisplatin) | PD-L1 negative, MSS | 9 | 9 | 9 | PR | 3.9 | 3.9 | ||
cervical carcinoma | ||||||||||||
001-027 | Cohort 2 | Adenocarcinoma | 2nd line FOLFIRI | PD-L1: CPS 80%, MSS | 4 | 4 | 4 | PD | 1.8 | 12.3 | ||
GEJ Typ II | ||||||||||||
001-028** | Cohort 2 | Adenocarcinoma | 2nd line FOLFIRI | PD-L1: nk; MSS, RAS | 4 | 4 | 4 | PD | 1.9 | 11.8 | ||
rectum | and BRAF wt | |||||||||||
* clinical progression, no response data according o RECIST 1.1 existing; ** low PD-L1 and MSS stable;
nk = not known; SD = stable disease; PD = progressive disease; PR = partial response; response = acc. RECIST 1.1 TPS = tumor proportion score; CPS = combined positivity score
Results
The trial was completed with 12 patients (cohort 1: gastric, gallbladder, colon,
pleural mesothelioma; cohort 2: gastric, gastroesophageal, anal, rectum, cervix uteri).
No dose limiting toxicities occurred. With data cut off from 14-May-2021, 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 ileus 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, 47 adverse events (AEs; grade 1-2, 29; grade 3, 14; grade 4, 3; grade 5, 1) occurred in 5 pts. Most common grade 1-2 AEs were nausea, pain in 33%, 33% of the pts. Most common grade 3 AEs were ileus, vomiting in 33%, 33% of the pts. 2 AEs grade 4 (hearing impaired, sepsis) and 1 AE grade 5 (acute renal insufficiency) were reported. All AEs grade 3-5 were considered causally unrelated.
In coh 2, 51 adverse events (AEs; grade 1-2, 29; grade 3, 19; grade 4, 2; grade 5, 1) occurred in 5 pts. The most common grade 1-2 AE was hypothyroidism in 33% of the pts. 1 AE grade 5 (diffuse myocardial fibrosis) was reported. Only 1 AE grade 3-5 was considered causally related (urinary tract infection grade 3 related with avelumab).
5 pts showed partial response as best response (2 coh 1: colon, pleural
mesothelioma; 3 coh 2: gastric, anal, cervical), 1 stable disease with clinical progression (coh 2) (all but one of these pts still alive), 5 disease progressions acc. to RECIST 1.1 (3 coh 1, 2 coh 2), 1 clinical progression (coh 1).
Activity was also observed in pre-treatednon-immunogenictumors. In the entire study population 75% were still alive, 66.7% of cohort 1, 83.3% of cohort 2.
Table 2: Summarized SAEs by patients
SAE | Cohort 1 | Cohort 2 | Total | |||
800mg avelumab + 6mg efti | 800mg evelumab + 30mg efti | |||||
n=6 (%) | n=6 (%) | n=12 (%) | ||||
Patients with at least one SAE | 3 | (50%) | 4 | (67%) | 7 | (58%) |
Patients with at least one SAE | 0 | (0%) | 0 | (0%) | 0 | (0%) |
with relation to study treatment | ||||||
First author conflicts of interest
TOG had an advisory role for Lilly, MSD Oncology, Bayer, SERVIER, BMS and Roche, served as speaker for Lilly, MSD, Servier, and received research funding from Deutsche Foraschungsgemeinschaft, Deutsche Krebshilfe, Gemeinsamer Bundesausschuss and AstraZeneca
Eye pain | 1 | (17%) | 1 | (8%) | |
Hearing impaired | 1 (17%) | 1 (8%) | |||
Feeding tube dislocation | 1 | (17%) | 1 | (8%) | |
Skin infection | 1 (17%) | 1 (8%) |
Table 4: Most common adverse events (irrespective of relationship to study drug)
Cohort 1 | Cohort 2 | |||
800mg avelumab + 6mg efti | 800mg avelumab + 30mg efti | |||
n=6 (%) | n=6 (%) | |||
Most common AEs | G1/G2 | G3 | G1/G2 | G3 |
Pain | 3 (50%) | 1 (17%) | 2 (33%) | |
Nausea/Vomiting | 2 (33%) | 2 (33%) | 1 (17%) | |
Injection site reaction | 1 (17%) | 1 (17%) | ||
Ileus | 2 (33%) | |||
Chills | 1 (17%) | 1 (17%) | ||
Fever | 1 (17%) | 1 (17%) | ||
Hypokalemia | 1 (17%) | 1 (17%) | ||
CRP increased | 1 (17%) | 1 (17%) | ||
Dysphagia | 1 (17%) | 1 (17%) | ||
Hypothyroidism | 2 (33%) |
Table 5: Treatment related AEs
Cohort 1 | Cohort 2 | ||||||||
800mg avelumab + 6mg efti | 800mg avelumab + 30mg efti | ||||||||
n=6 (%) | n=6 (%) | ||||||||
G1/G2 | G3 G4 G5 | G1/G2 | G3 | G4 G5 | |||||
Adverse reaction | Causality | Causality | Causality | Causality | Causality | Causality | Causality | Causality | Causality |
efti | avelumab | efti and avelumab | efti | avelumab efti and avelumab | efti | avelumab efti and avelumab | |||
Chills | 1 (17%) | 1 (17%) | |||||||
CRP increased | 1 (17%) | ||||||||
Dry eye | 1 (17%) | ||||||||
Dyspnea | 1 (17%) | ||||||||
Fever | 1 (17%) | 1 (17%) | |||||||
Hypotension | 1 (17%) | ||||||||
Hypothyroidism | 2 (33%) | ||||||||
Injection site reaction | 1 (17%) | 1 (17%) | |||||||
Lipohypertrophy | 1 (17%) | ||||||||
Nausea | 1 (17%) | ||||||||
Sarcoidosis | 1 (17%) | ||||||||
Urinary tract infection | 1 (17%) |
Conclusion
Combination treatment with avelumab 800mg and efti 6mg (cohort 1) or 30 mg (cohort 2) is well tolerated, with promising signals of efficacy. No unexpected AEs were observed in the combination. In both cohorts, first signals of therapeutic efficacy were detectable which will be further evaluated.
First author contact information: | • | Study supported by Immutep GmbH (grant/IMP) |
Thorsten O. Goetze, goetze.thorsten@ikf-khnw.de | ||
• | Avelumab was provided by Pfizer, as part of an alliance | |
Study management contact information: | between Pfizer and Merck (CrossRef Funder ID: | |
Regina Eickhoff, eickhoff.regina@ikf-khnw.de | 10.13039/100009945) |
Study identifiers:EudraCT-No.:2016-002309-20, Clinicaltrials.gov: NCT03252938
Attachments
- Original document
- Permalink
Disclaimer
Immutep Ltd. published this content on 20 September 2021 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 20 September 2021 18:11:05 UTC.
