sabestomig (AZD7789) / AstraZeneca - LARVOL DELTA

Safety and preliminary efficacy of AZD7789, a bispecific antibody targeting PD-1 and TIM-3, in patients (pts) with stage IIIB–IV non-small-cell lung cancer (NSCLC) with previous anti-PD-(L)1 therapy (ESMO 2023) - P1/2 | "Conclusions AZD7789 has manageable safety and shows preliminary efficacy at tolerable doses. Evaluation is ongoing in immunotherapy-naive pts with NSCLC and pts with acquired resistance to immunotherapy."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HAVCR2

SAFETY AND EFFICACY RESULTS FROM AN OPEN-LABEL PHASE 1/2 TRIAL OF SABESTOMIG (AZD7789) IN PATIENTS WITH RELAPSED/REFRACTORY CLASSICAL HODGKIN LYMPHOMA PREVIOUSLY TREATED WITH ANTI-PD-(L)1 THERAPIES (EHA 2024) - P1/2 | "Sabestomig has a manageable safety profile at doses up to 2000 mg, with evidence of effective antitumoractivity in heavily pretreated pts with cHL who were refractory to or relapsed after prior anti-PD(L)1 treatment. These data suggest that blockade of TIM-3 can reinvigorate antitumor responses in these pts. Furtherinvestigation of sabestomig in cHL is warranted."

Clinical • P1/2 data • Bone Marrow Transplantation • Fatigue • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • Pain • Transplantation • HAVCR2

TROPION-Lung04: Phase 1b Study of Dato-DXd in Combination With Immunotherapy With or Without Carboplatin in Advanced or Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=155 | Active, not recruiting | Sponsor: AstraZeneca | Trial completion date: May 2026 ➔ May 2027

Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • KRAS

MST01-AZN-05: PBI-MST-01 (NCT04541108) Substudy AZN-05: Intratumoral Microdosing of Rilvegostomig, Volrustomig, Sabestomig, and AZD9592 in HNSCC (clinicaltrials.gov) - P1 | N=17 | Completed | Sponsor: Presage Biosciences | Recruiting ➔ Completed | Trial completion date: Apr 2025 ➔ Mar 2026 | Trial primary completion date: Feb 2025 ➔ Mar 2026

Trial completion • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Phase 0 Master Protocol for CIVO Intratumoral Microdosing of Anti-Cancer Therapies (clinicaltrials.gov) - P1 | N=15 | Active, not recruiting | Sponsor: Presage Biosciences | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Safety and Preliminary Efficacy of Sabestomig (AZD7789), an Anti-PD-1 and Anti-TIM-3 Bispecific Antibody, in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma Previously Treated with Anti-PD-(L)1 Therapy (ASH 2023) - P1 | "Sabestomig is intravenously infused over 1 hour following pretreatment with diphenhydramine and acetaminophen every 3 weeks, with planned doses ranging from 2 to 2000 mg across 8 cohorts (A1–A8); cohorts A1 to A4 (2, 7, 22.5 or 75 mg) follow an accelerated titration design with a single patient treated at each dose level, while cohorts A5 to A8 (225–2000 mg) follow a modified toxicity probability interval-2 algorithm. Early efficacy data at 750 mg is encouraging with objective responses in 3/3 patients who had their first disease assessment, including those who were anti-PD-1 refractory or who relapsed on treatment. Updated data will be presented from ongoing and subsequent patients treated during dose escalation with doses of up to 2000 mg."

Clinical • IO biomarker • Classical Hodgkin Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Infectious Disease • Lymphoma • Oncology • Peptic Ulcer • Septic Shock • Solid Tumor • HAVCR2

D9571C00001: Safety and Preliminary Efficacy Assessment of AZD7789 in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=45 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion • Classical Hodgkin Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology

TROPION-Lung04: Phase 1b Study of Dato-DXd in Combination With Immunotherapy With or Without Carboplatin in Advanced or Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=165 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting | N=371 ➔ 165 | Trial completion date: Jan 2026 ➔ Apr 2026 | Trial primary completion date: Jan 2026 ➔ Apr 2026

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • PD-L1

GEMINI-Gastric: Novel Combinations in Participants With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (clinicaltrials.gov) - P2 | N=240 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Jan 2027 ➔ Jul 2027 | Trial primary completion date: Jan 2026 ➔ Jul 2026

Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • CLDN18

AstraZeneca CEO defends 'fantastic' Alexion buyout in face of $753M hit from dropped drug (FierceBiotech) - "Sabestomig, a PD-1xTIM3 bispecific antibody, was the other victim of AstraZeneca’s strategic portfolio prioritization. The company was testing the candidate in patients with lung and gastric cancers in a phase 1/2a trial but stopped enrollment well short of its target in December. Data did for the other two programs. AstraZeneca scrapped a phase 2 trial of anti-LIF antibody AZD0171 in pancreatic cancer because of efficacy data, although it still lists the asset as part of the multiregimen NeoCOAST-2 trial."

Enrollment status • Trial termination • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma

GEMINI-Gastric: Novel Combinations in Participants With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (clinicaltrials.gov) - P2 | N=240 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Mar 2026 ➔ Jan 2027 | Trial primary completion date: Sep 2025 ➔ Jan 2026

Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • CLDN18

D9571C00001: Safety and Preliminary Efficacy Assessment of AZD7789 in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=45 | Active, not recruiting | Sponsor: AstraZeneca | Phase classification: P1/2 ➔ P1

Phase classification • Classical Hodgkin Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology

A Study to Assess the Safety and Efficacy of AZD7789 in Participants With Advanced or Metastatic Solid Cancer (clinicaltrials.gov) - P1/2 | N=136 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting | N=232 ➔ 136 | Trial primary completion date: Aug 2026 ➔ Dec 2024

Enrollment change • Enrollment closed • Metastases • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

The PD1-TIM3 bispecific antibody sabestomig combines with a topoisomerase 1 inhibitor-conjugated ADC for additive anti-tumor activity and tumor immune modulation in a novel humanized NSCLC mouse model (SITC 2024) - "Conclusions Our data suggests that a novel bispecific immunotherapy targeting PD-1 and TIM-3 combined with a topoisomerase ADC modulates the TME leading to increased tumor immune infiltration, activation and anti-tumor response. Ethics Approval The animals run in these in vivo studies were humanely treated and housed according to Institutional Animal Care and Use Committee approved protocols (AUP-22-17) in the Laboratory Animal Resources facility at AstraZeneca, an Association for Animal Accreditation of Laboratory Animal Care and USA Department of Agriculture-licensed facility."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD34 • CD8 • CSF2 • CTLA4 • GZMB • HAVCR2 • HLA-C • IFNA1 • IFNG • PD-1

D9571C00001: Safety and Preliminary Efficacy Assessment of AZD7789 in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma (clinicaltrials.gov) - P1/2 | N=45 | Active, not recruiting | Sponsor: AstraZeneca | Trial completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology

D9571C00001: Safety and Preliminary Efficacy Assessment of AZD7789 in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma (clinicaltrials.gov) - P1/2 | N=45 | Active, not recruiting | Sponsor: AstraZeneca | Trial completion date: Oct 2027 ➔ Dec 2024 | Trial primary completion date: Feb 2026 ➔ Aug 2024

Trial completion date • Trial primary completion date • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology

A Study to Assess the Safety and Efficacy of AZD7789 in Participants With Advanced or Metastatic Solid Cancer (clinicaltrials.gov) - P1/2 | N=232 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Jul 2025 ➔ Aug 2026 | Trial primary completion date: Jul 2025 ➔ Aug 2026

Metastases • Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

GEMINI-Gastric: A phase 2 study of novel treatment combinations in patients with locally advanced unresectable or metastatic gastric cancers. (ASCO 2024) - P2 | "Novel agents include: volrustomig, an anti-PD-1/CTLA-4 bispecific humanized IgG1 monoclonal antibody (mAb); rilvegostomig, an anti-PD-1/TIGIT bispecific humanized IgG1 mAb; AZD0901, a claudin18.2-targeted antibody-drug conjugate; and AZD7789, an anti-PD-1/TIM-3 bispecific mAb. Sample sizes have been selected to provide adequate precision for the primary endpoints. The study is currently recruiting at sites in the US, Europe, and Asia."

Clinical • IO biomarker • Metastases • P2 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • CLDN18 • HAVCR2 • HER-2 • TIGIT

Safety and Preliminary Efficacy Assessment of AZD7789 in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma (clinicaltrials.gov) - P1/2 | N=45 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting | N=180 ➔ 45 | Trial primary completion date: Aug 2026 ➔ Feb 2026

Enrollment change • Enrollment closed • Trial primary completion date • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology

MST01-AZN-05: PBI-MST-01 (NCT04541108) Substudy AZN-05: Intratumoral Microdosing of Rilvegostomig, Volrustomig, and Sabestomig in HNSCC (clinicaltrials.gov) - P1 | N=15 | Recruiting | Sponsor: Presage Biosciences | Not yet recruiting ➔ Recruiting

Enrollment open • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

PBI-MST-01 (NCT04541108) Substudy AZN-05: Intratumoral Microdosing of Rilvegostomig, Volrustomig, and Sabestomig in HNSCC (clinicaltrials.gov) - P1 | N=15 | Not yet recruiting | Sponsor: Presage Biosciences

New P1 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

A Study to Assess the Safety and Efficacy of AZD7789 in Participants With Advanced or Metastatic Solid Cancer (clinicaltrials.gov) - P1/2 | N=232 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Apr 2025 ➔ Jul 2025 | Trial primary completion date: Jan 2025 ➔ Jul 2025

Metastases • Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study to Assess the Safety and Efficacy of AZD7789 in Participants With Advanced or Metastatic Solid Cancer (clinicaltrials.gov) - P1/2 | N=192 | Recruiting | Sponsor: AstraZeneca | N=147 ➔ 192

Enrollment change • Metastases • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

TROPION-Lung04: Phase 1b Study of Dato-DXd in Combination With Immunotherapy With or Without Carboplatin in Advanced or Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=321 | Recruiting | Sponsor: AstraZeneca | Phase classification: P1b ➔ P1 | N=232 ➔ 321

Combination therapy • Enrollment change • Metastases • Phase classification • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • PD-L1

Novel Combinations in Participants With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (clinicaltrials.gov) - P2 | N=240 | Recruiting | Sponsor: AstraZeneca | N=80 ➔ 240

Enrollment change • Metastases • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • CLDN18