SAR445710

P1, N=45, Terminated, Kadmon, a Sanofi Company | Trial completion date: Jul 2026 --> Dec 2023 | Recruiting --> Terminated | Trial primary completion date: Sep 2025 --> Dec 2023; Sponsor's decision.

P1, N=51, Recruiting, Kadmon, a Sanofi Company | N=80 --> 51

Enrolment continues in the QW schedule. Conclusions SAR445710 demonstrated a manageable toxicity profile with on-mechanism pharmacodynamics consistent with IL-15 agonism.

P1, N=80, Recruiting, Kadmon, a Sanofi Company | Trial completion date: Sep 2025 --> Dec 2026 | Trial primary completion date: Jul 2025 --> Feb 2026

Our data strongly points to a T cell memory response within the tumor draining lymph node as a possible driver of protection from systemic cancer recurrence, laying the groundwork for a new therapeutic strategy aimed at establishing CD8 immunosurveillance for protection from cancer recurrence.

We hypothesized that targeting the immune repertoire of the tumor draining lymph node (TDLN) with a memory inducing IL-15-PDL1 bispecific antibody (KD033) would establish immunosurveillance and decrease metastatic recurrence... Our data suggests that an Il-15/anti-PD1 neoadjuvant treatment strategy maintains an optimal response to metastatic recurrence. Promoting T-cell memory in the TDLN through IL-15-based immunomodulation may increase immunosurveillance and thus improve overall survival providing a rationale for an upcoming neoadjuvant clinical trial.

Kadmon has established a bi-functional cytokine fusion antibody platform, including KD033 (anti-PD-L1/IL15) and KD050 (anti-PD-1/IL15) fusion antibody, to extend the IL15 serum half-life and direct its action to tumors and/or T cells in the tumor microenvironment (TME). Legal entity responsible for the study Kadmon Corporation LLC. Funding Kadmon Corporation LLC.

Conclusions Increased in vitro IFNγ secretion from KD033-treated macrophages correlated with increased CD68/IFNγ double positive cell infiltrations in PD-L1 negative MC38 tumors from KD033-treated human PD-1/PD-L1 transgenic mice as evaluated by IHC. We hypothesized that our anti-PD-L1/IL15 KD033 induces anti-tumor immunity in PD-L1 negative tumors by activating PD-L1-expressing immune cells such as macrophages in the tumor microenvironment.

One patient (adenoid cystic carcinoma) in C1 was shown to have stable disease for more than 6 months and one patient (metastatic gastric adenocarcinoma) in C3 was shown to have stable disease for more than 4 months. Conclusions To date, KD033 has been well tolerated in all subjects with on-mechanism pharmacodynamics consistent with IL-15 agonism.

These showed that the efficacy of anti-PD-L1-IL-15 fusion protein is not limited to PD-L1 tumor expression as KD033 was efficacious in both PD-L1 positive and negative tumors.

These results showed that the efficacy of anti-PD-L1-IL-15 fusion protein is not limited to PD-L1 tumor expression as KD033 was efficacious in both PD-L1 positive and negative tumors . Mol Cancer Ther February 1 2021 (20) (2) 347-356; DOI: 10.1158/1535-7163.MCT-20-0457

KD033 has been well tolerated early in dose escalation with on-mechanism pharmacodynamics consistent with IL-15 agonism.