S95018 / 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

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

Phase 1b/2 Platform Study of Select Immunotherapy Combinations in Participants With Advanced Non-small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P1/2 | N=100 | Active, not recruiting | Sponsor: Servier Bio-Innovation LLC | N=74 ➔ 100

Enrollment change • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Phase 1b/2 Platform Study of Select Immunotherapy Combinations in Participants With Advanced Non-small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P1/2 | N=74 | Active, not recruiting | Sponsor: Servier Bio-Innovation LLC | Recruiting ➔ Active, not recruiting | N=176 ➔ 74

Enrollment change • Enrollment closed • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Phase 1b/2 Platform Study of Select Immunotherapy Combinations in Participants With Advanced Non-small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P1/2 | N=176 | Recruiting | Sponsor: Servier Bio-Innovation LLC | Not yet recruiting ➔ Recruiting

Enrollment open • IO biomarker • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

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

Servier Data Presented at AACR Underscores Unwavering Dedication to Advancing Oncology R&D (PRNewswire) - P1b | N=148 | NCT04641871 | Sponsor: Symphogen A/S | "Servier...is poised to unveil promising preliminary data at the American Association for Cancer Research (AACR) Annual Meeting 2024....Noteworthy, research also includes a Phase 1b multicenter study of anti-TIM3 (S095018, Sym023) in combination with anti-PD1 in patients with advanced/metastatic biliary duct cancer, which illustrates the safety of the combination as well as early anti-tumor activity."

P1 data • Biliary Cancer • Biliary Tract Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Servier Data Presented at AACR Underscores Unwavering Dedication to Advancing Oncology R&D (PRNewswire) - P1 | N=148 | NCT04641871 | "Noteworthy, research also includes a Phase 1b multicenter study of anti-TIM3 (S095018, Sym023) in combination with anti-PD1 in patients with advanced/metastatic biliary duct cancer, which illustrates the safety of the combination as well as early anti-tumor activity."

P1 data • Biliary Tract Cancer • Oncology • Solid Tumor

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

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

[VIRTUAL] Phase I studies of Sym021, an anti-PD-1 antibody, alone and in combination with Sym022 (anti-LAG-3) or Sym023 (anti-TIM-3) (ESMO 2020) - P1 | "Funding: Symphogen. Clinical trial identification: NCT03311412; NCT03489369; NCT03489343."

Combination therapy • IO biomarker • P1 data • Hematological Malignancies • Oncology • Solid Tumor

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 | Active, not recruiting | Sponsor: Symphogen A/S | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Biliary Tract Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gallbladder Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR2 • IDH1

Sym021 Monotherapy, in Combination With Sym022 or Sym023, and in Combination With Both Sym022 and Sym023 in Patients With Advanced Solid Tumor Malignancies or Lymphomas (clinicaltrials.gov) - P1 | N=91 | Completed | Sponsor: Symphogen A/S | Active, not recruiting ➔ Completed | Trial completion date: Oct 2022 ➔ Mar 2022 | Trial primary completion date: Oct 2022 ➔ Mar 2022

Combination therapy • Monotherapy • Trial completion • Trial completion date • Trial primary completion date • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

Sym021 Monotherapy, in Combination With Sym022 or Sym023, and in Combination With Both Sym022 and Sym023 in Patients With Advanced Solid Tumor Malignancies or Lymphomas (clinicaltrials.gov) - P1; N=91; Active, not recruiting; Sponsor: Symphogen A/S; Recruiting ➔ Active, not recruiting; Trial completion date: Nov 2021 ➔ Oct 2022; Trial primary completion date: Nov 2021 ➔ Oct 2022

Clinical • Combination therapy • Enrollment closed • Monotherapy • Trial completion date • Trial primary completion date • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

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; Active, not recruiting; Sponsor: Symphogen A/S; N=200 ➔ 100

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

Sym021 in Combination With Either Sym022 or Sym023 in Patients With Advanced Solid Tumor Malignancies (clinicaltrials.gov) - P1b; N=200; Active, not recruiting; Sponsor: Symphogen A/S; Recruiting ➔ Active, not recruiting

Clinical • Combination therapy • Enrollment closed • Cholangiocarcinoma • Endometrial Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Sym021 in Combination With Either Sym022 or Sym023 in Patients With Advanced Solid Tumor Malignancies (clinicaltrials.gov) - P1b; N=200; Recruiting; Sponsor: Symphogen A/S

Clinical • Combination therapy • New P1 trial • Cholangiocarcinoma • Endometrial Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Sym023 (Anti-TIM-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas (clinicaltrials.gov) - P1; N=24; Completed; Sponsor: Symphogen A/S; Active, not recruiting ➔ Completed; Trial completion date: Sep 2020 ➔ Jun 2020

Clinical • Trial completion • Trial completion date • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

Sym021 Monotherapy and in Combination With Sym022 or Sym023 in Patients With Advanced Solid Tumor Malignancies or Lymphomas (clinicaltrials.gov) - P1; N=102; Recruiting; Sponsor: Symphogen A/S; Trial completion date: Nov 2020 ➔ Nov 2021; Trial primary completion date: Nov 2019 ➔ Nov 2021

Clinical • Combination therapy • Monotherapy • Trial completion date • Trial primary completion date

Sym023 (Anti-TIM-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas (clinicaltrials.gov) - P1; N=24; Active, not recruiting; Sponsor: Symphogen A/S; Trial primary completion date: Dec 2019 ➔ Jun 2020

Clinical • Trial primary completion date

Sym023 (Anti-TIM-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas (clinicaltrials.gov) - P1; N=24; Active, not recruiting; Sponsor: Symphogen A/S; Recruiting ➔ Active, not recruiting; N=48 ➔ 24

Clinical • Enrollment change • Enrollment closed

Sym021 Monotherapy and in Combination With Sym022 or Sym023 in Patients With Advanced Solid Tumor Malignancies or Lymphomas (clinicaltrials.gov) - P1; N=102; Recruiting; Sponsor: Symphogen A/S; Trial primary completion date: May 2019 ➔ Nov 2019

Clinical • Combination therapy • Monotherapy • Trial primary completion date