1004P - Initial results from a phase I study of Nous-209, an off-the-shelf viral vectored immunotherapy encoding 209 shared frame shift peptide neoantigens, with pembrolizumab, for the treatment of tumors with a deficiency in mismatch repair/microsatellite instability

Background

Defective DNA mismatch repair (dMMR) leads to high levels of microsatellite-instability (MSI-H) and insertions or deletions in coding regions, resulting in the generation of tumor-specific frameshift peptides (FSPs). We selected 209 shared FSPs among patients with first- or second-line metastatic dMMR/MSI-H colorectal (CRC), gastric, and gastroesophageal junction (GEJ) cancers, to develop an off-the-shelf therapeutic vaccine. Nous-209, is a polyvalent viral vectored vaccine composed of 4 Great Apes Adenoviral (GAd) and 4 Modified Vaccinia Ankara (MVA) vectors (Leoni et al, Cancer Res. 2020).

Methods

Objectives of this phase I first in human (FIH) study (NCT04041310) of Nous-209 and pembrolizumab, a programmed death receptor-1 (PD-1)-inhibitor, include evaluation of safety, tolerability, immunogenicity, and preliminary efficacy of the combination. Nous-209 is administered intramuscularly, concomitantly with pembrolizumab (doses and schedule per approved label): 1 prime (GAd-209-FSP) at the 2^nd pembrolizumab infusion and 3 booster (MVA-209-FSP) injections at subsequent infusions each 3 weeks apart. The study is composed of two sequential cohorts: dose escalation and dose expansion.

Results

The first six patients (CRC, n=3; gastric and GEJ, n=3) were enrolled equally in two dose levels with median follow-up of 12.9 months (range 8.0 -19.0 months) as of April 30, 2021. No dose limiting toxicities (DLTs) were observed, and the treatment combination appears to be safe and tolerable. Vaccine immunogenicity was demonstrated by ex-vivo interferon-gamma ELIspot assay in 83% of patients. RECIST1.1 overall response rate was 67%: 4 partial responses (PR), 1 stable disease (SD) and 1 progressive disease (PD).

Conclusions

Combination of the Nous-209 genetic polyvalent cancer vaccine and pembrolizumab has been demonstrated to be safe, immunogenic, and has early signs of clinical efficacy, which may be attributed to the relative vaccine contribution.

Clinical trial identification

NCT04041310.

Editorial acknowledgement

Legal entity responsible for the study

Nouscom AG.

Funding

Nouscom AG.

Disclosure

G. Leoni: Financial Interests, Personal, Full or part-time Employment: Nouscom SRL. A.M. D'Alise: Financial Interests, Personal, Full or part-time Employment: Nouscom SRL. G. Cotugno: Financial Interests, Personal, Full or part-time Employment: Nouscom SRL. F. Langone: Financial Interests, Personal, Full or part-time Employment: Nouscom SRL. S. Capone: Financial Interests, Personal, Full or part-time Employment: Reithera SRL. M. Del Sorbo: Financial Interests, Personal, Full or part-time Employment: Reithera SRL. P. Delaite: Financial Interests, Personal, Full or part-time Employment: Nouscom AG. T. Faivre: Financial Interests, Personal, Full or part-time Employment: Nouscom AG. E. Scarselli: Financial Interests, Personal, Full or part-time Employment: Nouscom SRL. All other authors have declared no conflicts of interest.