SAR445710 / Sanofi - LARVOL DELTA

A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of KD033 (SAR445710) in Subjects With Metastatic or Locally Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=45 | Terminated | Sponsor: Kadmon, a Sanofi Company | Trial completion date: Jul 2026 ➔ Dec 2023 | Recruiting ➔ Terminated | Trial primary completion date: Sep 2025 ➔ Dec 2023; Sponsor's decision.

Metastases • Trial completion date • Trial primary completion date • Trial termination • Oncology • Solid Tumor

A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of KD033 (SAR445710) in Subjects With Metastatic or Locally Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=51 | Recruiting | Sponsor: Kadmon, a Sanofi Company | N=80 ➔ 51

Enrollment change • Oncology • Solid Tumor

Phase I dose escalation of SAR445710, a PDL1-IL15 targeted cytokine in metastatic and/or advanced solid tumors (SITC 2023) - P1 | "Enrolment continues in the QW schedule. Conclusions SAR445710 demonstrated a manageable toxicity profile with on-mechanism pharmacodynamics consistent with IL-15 agonism."

IO biomarker • Metastases • P1 data • Oncology • Solid Tumor • CD8 • IL15 • PD-L1

A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of KD033 (SAR445710) in Subjects With Metastatic or Locally Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: Kadmon, a Sanofi Company | Trial completion date: Dec 2026 ➔ Jul 2026 | Trial primary completion date: Feb 2026 ➔ Sep 2025

Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of KD033 (SAR445710) in Subjects With Metastatic or Locally Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: Kadmon, a Sanofi Company | Trial completion date: Oct 2025 ➔ Dec 2026 | Trial primary completion date: Jul 2025 ➔ Feb 2026

Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of KD033 (SAR445710) in Subjects With Metastatic or Locally Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: Kadmon, a Sanofi Company | Trial completion date: Dec 2026 ➔ Oct 2025 | Trial primary completion date: Feb 2026 ➔ Jul 2025

Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of KD033 (SAR445710) in Subjects With Metastatic or Locally Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: Kadmon, a Sanofi Company | Trial completion date: Sep 2025 ➔ Dec 2026 | Trial primary completion date: Jul 2025 ➔ Feb 2026

Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

A tumor draining lymph node CD8 T cell memory response is pivotal for a decrease in recurrence after neoadjuvant anti PD-1 therapy for NSCLC (AACR 2023) - "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."

Clinical • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • CXCR5

A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of KD033 (SAR445710) in Subjects With Metastatic or Locally Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: Kadmon, a Sanofi Company | N=50 ➔ 80

Enrollment change • Metastases • Oncology • Solid Tumor

A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of KD033 in Subjects With Metastatic or Locally Advanced Solid Tumors. (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Kadmon, a Sanofi Company | Trial completion date: Aug 2023 ➔ Sep 2025 | Trial primary completion date: Aug 2023 ➔ Sep 2025

Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Evaluation of the clinical molecule anti-human-PD-L1/IL-15 KD033 in the human-PD-1/PD-L1-expressing murine model demonstrates PD-L1 targeting of IL-15 in vivo. (PubMed, Cancer Immunol Immunother) - "Cytotoxic and myeloid cell signatures were upregulated in both tumors with relatively greater increases observed in hPDL1- MC38 tumors. These effects of KD033 treatment in PD-L1 positive and negative tumors demonstrate the role of PD-L1 in targeting of IL-15 cytokine in vivo."

Journal • Preclinical • Immune Modulation • Immunology • Inflammation • Oncology • IL15

Neoadjuvant IL-15-PDL1 Antibody Promotes T cell Memory and Decreases Metastatic Recurrence in Resectable NSCLC (IASLC-WCLC 2022) - "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."

Clinical • Immune Modulation • Immunology • Inflammation • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD44 • CD8 • CXCR5 • IL15

Phase I dose escalation of KD033, a PDL1-IL15 bispecific molecule, in metastatic and advanced solid tumors (SITC 2021) - P1 | "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."

P1 data • Adenoid Cystic Carcinoma • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD8 • IL15 • IL2 • PD-L1

A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of KD033 in Subjects With Metastatic or Locally Advanced Solid Tumors. (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Kadmon Corporation, LLC | Trial completion date: Mar 2023 ➔ Aug 2023 | Trial primary completion date: Nov 2022 ➔ Aug 2023

Trial completion date • Trial primary completion date • Oncology • Solid Tumor

KD033, a PDL1-1L15 bispecific molecule for the treatment of cancer (YouTube) - "Jason Luke, MD...describes the mechanism of action of the PDL1-IL15 bispecific molecule, KD033. Early dose-escalation clinical trial data of PDL1-IL15 have demonstrated responses in the form of fevers and chills and even disease regression in some patients. This interview took place during the 36th Society for Immunotherapy of Cancer (SITC) Annual Meeting in Washington, D.C."

Interview • Video

A novel bi-functional IL15 cytokine fusion antibody selected to kill B7-H4 positive tumor cells (ESMO-IO 2021) - "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."

IO biomarker • Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • CD8 • IL15 • IL2 • STAT5 • VTCN1

Anti-PD-L1/IL-15 KD033 activated macrophages and induced anti-tumor immunity in the tumor-microenvironment (SITC 2021) - "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."

Biomarker • IO biomarker • Tumor microenvironment • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • CD68 • CD8 • IFNG • IL15

Kadmon Announces Abstracts Accepted for Presentation at the Society for Immunotherapy of Cancer's 36th Annual Meeting (Issuer Direct) - "Kadmon Holdings, Inc...announced it will present data from the ongoing Phase 1 clinical trial of KD033, its anti-PD-L1/IL-15 fusion protein, in patients with metastatic or locally advanced solid tumors, in addition to other IL-15 preclinical work, at the Society for Immunotherapy of Cancer's (SITC 2021) 36th Annual Meeting, taking place virtually November 10 - 14, 2021."

P1 data • Oncology • Solid Tumor

[VIRTUAL] Preclinical evaluation of KD033, a human anti-PD-L1/IL-15 bispecific protein, in human PD-1/PD-L1 transgenic C57/Bl6 mice with PD-L1 positive and negative tumors (ESMO 2021) - "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."

IO biomarker • Preclinical • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • CD8 • IL15 • PD-1

[VIRTUAL] Phase I dose escalation of KD033, a PDL1-IL15 bispecific molecule, in advanced solid tumors. (ASCO 2021) - P1 | "KD033 has been well tolerated early in dose escalation with on-mechanism pharmacodynamics consistent with IL-15 agonism."

P1 data • Adenoid Cystic Carcinoma • Oncology • Solid Tumor • CD8 • IL15 • IL2 • PD-L1

[VIRTUAL] A phase 1 multiple ascending dose study to investigate the safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of KD033 in subjects with metastatic or locally advanced solid tumors (AACR 2021) - P1 | "Secondary objectives include characterization of PK and immunogenicity, evaluation of immune correlates that will potentially differentiate the impact of KD033 versus monotherapy as well as investigate IL-15 biology and determine best overall response and duration of response. (NCT04242147)"

Clinical • P1 data • PK/PD data • Oncology • Solid Tumor • IL15 • IL2

[VIRTUAL] Efficacy of KD033, an anti-human-PD-L1-IL-15 bispecific protein, in human-PD-L1 positive and negative murine tumor models. (ASCO 2021) - "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"

IO biomarker • Preclinical • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • Transplantation • CD8 • IL15 • PD-1

Kadmon to Present Initial Safety Data from Phase 1 Study of KD033 at the 2021 American Society of Clinical Oncology Annual Meeting (Issuer Direct) - P1, N=40; NCT04242147; Sponsor: Kadmon Corporation, LLC; “The KD033 data to be presented at ASCO includes initial safety results from the Phase 1 dose escalation portion of the KD033-101 clinical trial. Key highlights from the presentation include: Nine patients from the first three cohorts of the trial have been treated with KD033 doses up to 50 µg/kg as of April 21, 2021, with the longest exposure being 30 weeks; KD033 has been well tolerated, with no dose-limiting toxicities reported; Dose escalation continues; Additional clinical data from the KD033-101 trial will be available in Q4 2021.”

P1 data • Oncology • Solid Tumor

Kadmon Provides Business Update and Reports First Quarter 2021 Financial Results (Kadmon Press Release) - “KD033: Present initial safety data from the ongoing Phase 1 clinical trial of KD033, the Company's anti-PD-L1/IL-15 fusion protein, in patients with metastatic or locally advanced solid tumors, at the American Society of Clinical Oncology (ASCO) Annual Meeting, to be held June 4-8, 2021; additional clinical data from the trial are expected to be available in Q4 2021.”

P1 data • Oncology • Solid Tumor

Kadmon Announces Trial-In-Progress Poster on KD033 at the 2021 American Association for Cancer Research Annual Meeting (Yahoo Finance) - "Kadmon Holdings...announced it will present a trial-in-progress poster on KD033-101, the Company's ongoing dose-escalation, dose-expansion trial of KD033 in patients with metastatic and locally advanced solid tumors, at the 2021 American Association for Cancer Research (AACR) Annual Meeting, taking place virtually April 10 - 15, 2021...Initial safety data from the trial are anticipated in Q2 2021. Additional clinical data from the trial are anticipated in Q4 2021."

P1 data • Oncology • Solid Tumor