Sym021 / Servier - LARVOL DELTA

Phase Ib multicenter study of anti-TIM-3 (S095018/Sym023) in combination with anti-PD-1 (Sym021) in patients with advanced/metastatic recurrent biliary tract cancer. (PubMed, J Immunother Cancer) - P1 | "Dual PD-1/TIM-3 inhibition was tolerable but exhibited modest antitumor activity in patients with advanced/metastatic recurrent BTC who had not received prior anti-PD-(L)1 treatment."

Clinical • IO biomarker • Journal • P1 data • Biliary Cancer • Biliary Tract Cancer • Dermatology • Fatigue • Oncology • Pruritus • Solid Tumor • CD8 • IFNG • PD-L1 • PD-L2

A phase 1b multicenter study of anti-TIM3 (S095018/Sym023) in combination with anti-PD1 (Sym021) in patients with advanced/metastatic recurrent biliary tract cancer (AACR 2024) - P1 | "S095018 in combination with Sym021 exhibited antitumor activity in patients with advanced/metastatic recurrent biliary tract cancer who had not received prior treatment with PD-1/-L1 inhibitors. The combination was well tolerated without new safety signals. Further biomarker analysis is ongoing."

Clinical • Combination therapy • IO biomarker • Metastases • P1 data • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD8 • IFNG • PD-L2

Phase 1 multicenter study of the NKG2A targeting antibody S095029 as a single agent and in combination with anti-PD-1 in patients with advanced malignancies. (PubMed, J Immunother Cancer) - P1 | "The anti-NKG2A antibody S095029 in combination with anti-PD-1 Sym021 demonstrated a favorable safety profile and exhibited signal of antitumor activity in unselected, heavily pretreated patients with advanced malignancies."

Clinical • First-in-human • IO biomarker • Journal • P1 data • Leiomyosarcoma • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Unknown Primary • CXCL9 • HLA-E • KLRC1 • KLRD1 • TNFA

Sym021 in Combination With Either Sym022 or Sym023 or Sym023 and Irinotecan in Patients With Recurrent Advanced Biliary Tract Carcinomas (clinicaltrials.gov) - P1b; N=100; Recruiting; Sponsor: Symphogen A/S; Active, not recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Biliary Cancer • Biliary Tract Cancer • Gallbladder Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR2 • IDH1

Sym021 in Combination With Either Sym022 or Sym023 or Sym023 and Irinotecan in Patients With Recurrent Advanced Selected Solid Tumor Malignancies (clinicaltrials.gov) - P1b | N=148 | Recruiting | Sponsor: Symphogen A/S | N=100 ➔ 148 | Trial primary completion date: Dec 2024 ➔ Apr 2024

Combination therapy • Enrollment change • Trial primary completion date • Biliary Tract Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gallbladder Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR2 • IDH1

CL1-95029-001: S095029 as Monotherapy and in Combination With Sym021 in Patients With Advanced Solid Tumor Malignancies Followed by an Expansion Part With Triple Combinations in Patients With Metastatic Gastric or Colorectal Cancers (clinicaltrials.gov) - P1 | N=41 | Completed | Sponsor: Institut de Recherches Internationales Servier | Active, not recruiting ➔ Completed

Monotherapy • Trial completion • Colorectal Cancer • Gastric Cancer • Oncology • Solid Tumor

Molecular and early clinical characterization of the anti-CD73 antibody S095024 (Sym024) (AACR 2024) - P1 | "The clinical safety, tolerability, pharmacokinetics, and pharmacodynamics of S095024 alone or in combination with Sym021, an anti-PD1 antibody, was investigated in a first-in-human study (NCT04672434) in patients with selected types of advanced solid tumors. These findings reveal the potential of S095024 (Sym024) to prevent adenosine-mediated tumor evasion and support further clinical investigation."

Clinical • First-in-human • IO biomarker • Oncology • Solid Tumor • CD73 • ENTPD1 • NT5E

CL1-95029-001: S095029 as Monotherapy and in Combination With Sym021 in Patients With Advanced Solid Tumor Malignancies Followed by an Expansion Part With Triple Combinations in Patients With Metastatic Gastric or Colorectal Cancers (clinicaltrials.gov) - P1 | N=51 | Active, not recruiting | Sponsor: Institut de Recherches Internationales Servier | Trial completion date: Jun 2025 ➔ Mar 2026

Monotherapy • Trial completion date • Colorectal Cancer • Gastric Cancer • Oncology • Solid Tumor • BRAF • HER-2 • KRAS • NRAS

CL1-95029-001: S095029 as Monotherapy and in Combination With Sym021 in Patients With Advanced Solid Tumor Malignancies Followed by an Expansion Part With Triple Combinations in Patients With Metastatic Gastric or Colorectal Cancers (clinicaltrials.gov) - P1 | N=51 | Active, not recruiting | Sponsor: Institut de Recherches Internationales Servier | Trial completion date: Jan 2025 ➔ Jun 2025

Combination therapy • Metastases • Monotherapy • Trial completion date • Colorectal Cancer • Gastric Cancer • Oncology • Solid Tumor • BRAF • HER-2 • KRAS • NRAS

Sym024 Monotherapy and in Combination With Sym021 in Patients With Advanced Solid Tumor Malignancies (clinicaltrials.gov) - P1 | N=48 | Completed | Sponsor: Symphogen A/S | Active, not recruiting ➔ Completed

Combination therapy • Metastases • Monotherapy • Trial completion • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Head and Neck Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • MSI

A phase 1 multicenter study of the safety and efficacy of the NKG2A targeting antibody S095029 as single agent and in combination with anti-PD1 in patients with advanced malignancies (SITC 2024) - P1, P1/2 | "Sym021 is an anti-PD1 IgG1 antibody. S095029 is currently investigated in combination with anti-PD1 in patients with previously untreated advanced NSCLC with high PDL1 expression (NCT06162572), and in patients with MSI-H/dMMR advanced gastric/GEJ cancer (NCT06116136). Ethics Approval Written informed consent was provided by all the patients or their legal guardians before participation in the trial, and approval from the institutional review board or independent ethics committee was obtained at each trial site."

Clinical • Combination therapy • IO biomarker • Late-breaking abstract • Metastases • P1 data • Gastric Cancer • Leiomyosarcoma • Lung Cancer • Microsatellite Instability • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • CXCL9 • HLA-E • IFNG • KLRC1 • KLRD1 • MSI • PD-L1 • TNFA

S095029 as Monotherapy and in Combination With Sym021 in Patients With Advanced Solid Tumor Malignancies Followed by an Expansion Part With Triple Combinations in Patients With Metastatic Gastric or Colorectal Cancers (clinicaltrials.gov) - P1 | N=51 | Active, not recruiting | Sponsor: Institut de Recherches Internationales Servier | Trial completion date: Jul 2024 ➔ Jan 2025

Combination therapy • Metastases • Monotherapy • Trial completion date • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • HER-2 • KRAS • NRAS

Sym021 in Combination With Either Sym022 or Sym023 or Sym023 and Irinotecan in Patients With Recurrent Advanced Selected Solid Tumor Malignancies (clinicaltrials.gov) - P1 | N=78 | Completed | Sponsor: Symphogen A/S | Active, not recruiting ➔ Completed

Combination therapy • Metastases • Trial completion • Biliary Tract Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gallbladder Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR2 • IDH1

Sym021 in Combination With Either Sym022 or Sym023 or Sym023 and Irinotecan in Patients With Recurrent Advanced Selected Solid Tumor Malignancies (clinicaltrials.gov) - P1 | N=78 | Active, not recruiting | Sponsor: Symphogen A/S | N=148 ➔ 78 | Trial completion date: Jan 2025 ➔ Jun 2024

Combination therapy • Enrollment change • Metastases • Trial completion date • Biliary Tract Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gallbladder Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR2 • IDH1

Sym024 Monotherapy and in Combination With Sym021 in Patients With Advanced Solid Tumor Malignancies (clinicaltrials.gov) - P1 | N=48 | Active, not recruiting | Sponsor: Symphogen A/S | N=100 ➔ 48

Combination therapy • Enrollment change • Metastases • Monotherapy • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • MSI

Sym024 Monotherapy and in Combination With Sym021 in Patients With Advanced Solid Tumor Malignancies (clinicaltrials.gov) - P1 | N=100 | Active, not recruiting | Sponsor: Symphogen A/S | Trial completion date: Jul 2024 ➔ Dec 2024 | Trial primary completion date: Jul 2024 ➔ Dec 2024

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • MSI

S095029 as Monotherapy and in Combination With Sym021 in Patients With Advanced Solid Tumor Malignancies Followed by an Expansion Part With Triple Combinations in Patients With Metastatic Gastric or Colorectal Cancers (clinicaltrials.gov) - P1 | N=51 | Active, not recruiting | Sponsor: Institut de Recherches Internationales Servier | Trial completion date: Feb 2024 ➔ Jul 2024

Combination therapy • Metastases • Monotherapy • Trial completion date • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • HER-2 • KRAS • NRAS

Sym021 in Combination With Either Sym022 or Sym023 or Sym023 and Irinotecan in Patients With Recurrent Advanced Selected Solid Tumor Malignancies (clinicaltrials.gov) - P1 | N=148 | Active, not recruiting | Sponsor: Symphogen A/S | Phase classification: P1b ➔ P1

Phase classification • Biliary Tract Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gallbladder Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR2 • IDH1

S095029 as Monotherapy and in Combination With Sym021 in Patients With Advanced Solid Tumor Malignancies Followed by an Expansion Part With Triple Combinations in Patients With Metastatic Gastric or Colorectal Cancers (clinicaltrials.gov) - P1 | N=51 | Active, not recruiting | Sponsor: Institut de Recherches Internationales Servier | Recruiting ➔ Active, not recruiting

Enrollment closed • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • HER-2 • KRAS • NRAS

Sym024 Monotherapy and in Combination With Sym021 in Patients With Advanced Solid Tumor Malignancies (clinicaltrials.gov) - P1 | N=100 | Active, not recruiting | Sponsor: Symphogen A/S | Trial completion date: Dec 2023 ➔ Jul 2024 | Trial primary completion date: Dec 2023 ➔ Jul 2024

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • MSI

S095029 as Monotherapy and in Combination With Sym021 in Patients With Advanced Solid Tumor Malignancies Followed by an Expansion Part With Triple Combinations in Patients With Metastatic Gastric or Colorectal Cancers (clinicaltrials.gov) - P1 | N=41 | Recruiting | Sponsor: Institut de Recherches Internationales Servier | Phase classification: P1a/1b ➔ P1

Combination therapy • Metastases • Monotherapy • Phase classification • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • HER-2 • KRAS • NRAS

Sym024 Monotherapy and in Combination With Sym021 in Patients With Advanced Solid Tumor Malignancies (clinicaltrials.gov) - P1 | N=100 | Active, not recruiting | Sponsor: Symphogen A/S | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Monotherapy • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • MSI

S095029 as Monotherapy and in Combination With Sym021 in Patients With Advanced Solid Tumor Malignancies Followed by an Expansion Part With Triple Combinations in Patients With Metastatic Gastric or Colorectal Cancers (clinicaltrials.gov) - P1a/1b | N=39 | Recruiting | Sponsor: Institut de Recherches Internationales Servier | N=129 ➔ 39 | Trial completion date: Jul 2025 ➔ Jan 2024 | Trial primary completion date: May 2023 ➔ Jan 2024

Combination therapy • Enrollment change • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • HER-2 • KRAS • NRAS

Sym024 Monotherapy and in Combination With Sym021 in Patients With Advanced Solid Tumor Malignancies (clinicaltrials.gov) - P1 | N=100 | Recruiting | Sponsor: Symphogen A/S | Trial completion date: Jun 2024 ➔ Dec 2023 | Trial primary completion date: Jun 2024 ➔ Dec 2023

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • MSI

A phase I study of Sym021, an anti-PD-1 antibody (Ab), alone and in combination with Sym022 (anti-LAG-3) or Sym023 (anti-TIM-3) (ESMO 2019) - P1; "Sym021 alone was well tolerated and demonstrated both immune modulation and antitumor activity. Evaluation of single agent dose-escalation trials of Sym022 and Sym023 and of the Sym021/Sym022 and Sym021/Sym023 combination arms are ongoing. Results from these studies will be presented."

Combination therapy • P1 data • Gastric Cancer • Gastrointestinal Cancer • Hematological Malignancies • Lymphoma • Oncology