Safety and Preliminary Efficacy Assessment of AZD7789 in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma

A Phase I/II Open-label, Multi-center Study to Assess Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of AZD7789, an Anti-PD-1 and Anti-TIM-3 Bispecific Antibody, in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma.

The study is intended to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of sabestomig (AZD7789) in patients with relapsed/refractory classical Hodgkin Lymphoma (r/r cHL).

Study Overview

• Status: Completed
• Conditions: Relapsed or Refractory Classical Hodgkin Lymphoma
• Intervention / Treatment: Drug: Sabestomig (AZD7789)

Detailed Description

This is a Phase I/II, open-label multi-center study will have sabestomig administered via intravenous infusion on Cycle 1 Day 1 to adult/young adult patients with relapsed/refractory classical Hodgkin Lymphoma (r/r cHL). This study will have 2 parts: Phase 1 (Part A) Dose Escalation and Phase 2 (Part B) Dose Expansion.

Patients will be treated with study intervention for a maximum of 35 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent, or if other reasons to discontinue treatment occur.

The trial was intended to be Phase I/II trial (but the trial never moved forward to Phase 2). Hence, the study Phase was updated to Phase I.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X6
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Research Site
• Denmark
  • København Ø, Denmark, 2100
    • Research Site
• France
  • Lille, France, 59037
    • Research Site
• Italy
  • Bologna, Italy, 40138
    • Research Site
  • Napoli, Italy, 80131
    • Research Site
• Spain
  • Valencia, Spain, 46010
    • Research Site
• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • Research Site
  • Oxford, United Kingdom, 0X3 7LJ
    • Research Site
• United States
  • California
    • Duarte, California, United States, 91010
      • Research Site
  • Florida
    • Miami, Florida, United States, 33136
      • Research Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Research Site
  • New York
    • New York, New York, United States, 10065
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 101 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥ 16 years of age at the time of obtaining informed consent
• Eastern Cooperative Oncology Group performance status of 0 or 1 at screening
• At least one positron emission tomography (PET)-avid measurable lesion according to Modified Lugano Criteria after the last line of therapy.
• Confirmed histological diagnosis of active relapse/refractory cHL
• Failed at least 2 prior lines of systemic therapy.
• No previous treatment with anti-TIM-3.
• Adequate organ and bone marrow function
• Non-pregnant women and willingness of female patients to avoid pregnancy or male participants willing to avoid fathering children through highly effective methods of contraception
• Minimum body weight ≥ 40 kg for all participants.

Exclusion Criteria:

• Unresolved toxicities of ≥ Grade 2 from prior therapy
• Any prior ≥ Grade 3 imAE while receiving prior checkpoint inhibitor immunotherapy
• Patients with central nervous system (CNS) involvement or leptomeningeal disease.
• History of allogeneic stem cell transplant or organ transplantation.
• Any venous or arterial thromboembolic event within ≤ 6 months prior to the first dose of study intervention.
• Active infection including Tuberculosis (TB), human immunodeficiency virus (HIV), hepatitis A, chronic or active hepatitis B, chronic or active hepatitis C, active COVID-19 infection
• History of arrhythmia which is requires treatment, symptomatic or uncontrol led atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia
• Uncontrolled intercurrent illness.
• Active or prior documented pathologically confirmed autoimmune or inflammatory disorders.
• Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD
• Other invasive malignancy within 2 years prior to screening
• Congenital long QT syndrome or history of QT prolongation associated with other medications that cannot be changed or discontinued based on a cardiologist assessment
• Current or prior use of immunosuppressive medication within 14 days prior to the first dose of study intervention
• Any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: Dose Escalation; Patients with anti-PD-1/PD-L1 exposed r/r cHL will receive sabestomig to determine the recommended phase 2 dose (RP2D).	Drug: Sabestomig (AZD7789); Patients will receive sabestomig (PD-1/TIM-3 bispecific monoclonal antibody) via intravenous infusion.
Experimental: Cohort B1: Dose Expansion; Patients with anti-PD-1/PD-L1 exposed r/r cHL will receive sabestomig once the RP2D has been determined.	Drug: Sabestomig (AZD7789); Patients will receive sabestomig (PD-1/TIM-3 bispecific monoclonal antibody) via intravenous infusion.
Experimental: Cohort B2: Dose Expansion; Patients with anti-PD-1/PD-L1 naïve r/r cHL will receive sabestomig once the RP2D has been determined.	Drug: Sabestomig (AZD7789); Patients will receive sabestomig (PD-1/TIM-3 bispecific monoclonal antibody) via intravenous infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A (Dose Escalation): Number of Participants With Adverse Events (AEs)	The safety and tolerability of sabestomig in participants with r/r cHL were assessed.	From start of treatment [Cycle 1 Day 1 (C1D1) (each cycle was 28 days)] up to 90 days post last dose (approximately 2 years 5 months)
Part A (Dose Escalation): Number of Participants With Dose-limiting Toxicities (DLTs)	DLT was defined as any ≥Grade 3 AE as per NCI CTCAE version 5 unless unequivocally due to underlying malignancy or an extraneous cause. The following conditions were considered as DLTs: Any death not clearly due to the underlying disease or extraneous causes; Grade 4 imAE or anemia; Any ≥Grade 3 non-infectious pneumonitis or colitis of any duration; Specific liver transaminase elevation as per protocol; Any Grade 3 imAE, including rash, pruritus, or diarrhea, that does not downgrade to Grade 2 or less within 7 days; Grade 3 nausea, vomiting, or diarrhea that does not resolve to Grade 2 or less within 3 days of getting maximal supportive care; ≥Grade 3 neutropenia, without fever or systemic infection, that does not improve by at least one grade within 7 days; Grade 4 thrombocytopenia for more than 7 days or ≥Grade 3 thrombocytopenia along with Grade ≥2 bleeding; Grade 4 Cytokine Release Syndrome (CRS) of any duration or Grade 3 CRS not improving to Grade ≤2 within 72 hours	From first dose (C1D1) until 28 days for each participant [within 28 days DLT period]
Part B (Dose Expansion): Cohort B1: Objective Response Rate (ORR)	The anti-tumor activity of sabestomig in participants with r/r cHL was planned to be assessed. ORR was defined as the percentage of participants with an objective response [Best Overall Response of a complete response (CR) or partial response (PR)] as per modified Lugano criteria (Lugano 2014), with the denominator defined as the number of participants in the response-evaluable analysis set. Disease response was planned to be assessed according to Blinded Independent Central Review using modified Lugano criteria (Lugano 2014).	Up to approximately 2 years 90 days
Part B (Dose Expansion): Cohort B2: Complete Response Rate (CRR)	The anti-tumor activity of sabestomig in participants with r/r cHL was planned to be assessed. The CRR was defined as the percentage of participants with a CR as per modified Lugano criteria (Lugano 2014), with the denominator defined as the number of participants in the response-evaluable analysis set. Disease response was planned to be assessed according to Blinded Independent Central Review using modified Lugano criteria (Lugano 2014).	Up to approximately 2 years 90 days
Part B (Dose Expansion): Number of Participants With AEs	The safety and tolerability of sabestomig in participants with r/r cHL was planned to be assessed.	Up to approximately 2 years 90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A (Dose Escalation): Complete Response Rate (CRR)	The anti-tumor activity of sabestomig in participants with r/r cHL was assessed. The CRR was defined as the percentage of participants with a CR as per modified Lugano criteria (Lugano 2014) as assessed by the Investigator, with the denominator defined as the number of participants in the response-evaluable analysis set. Disease response was assessed according to Investigator assessment using modified Lugano criteria (Lugano 2014).	From start of treatment [C1D1 (each cycle was 28 days)] until first documented disease progression, or last evaluable assessment in the absence of progression (up to 2 years 5 months)
Part A (Dose Escalation): Objective Response Rate (ORR)	The anti-tumor activity of sabestomig in participants with r/r cHL was assessed. The ORR was defined as the percentage of participants with an objective response (Best Overall Response of CR or PR) as per modified Lugano criteria (Lugano 2014), as assessed by the Investigator, with the denominator defined as the number of participants in the response-evaluable analysis set. Disease response was assessed according to Investigator assessment using modified Lugano criteria (Lugano 2014).	From start of treatment [C1D1 (each cycle was 28 days)] until progression, or last evaluable assessment in the absence of progression (up to 2 years 5 months)
Part A (Dose Escalation): Duration of Response (DoR)	The anti-tumor activity of sabestomig in participants with r/r cHL was assessed. The DoR was defined as the time from the date of first documented objective response (CR or PR), as assessed by Investigator, using the modified Lugano criteria (Lugano 2014), until the date of first documented disease progression or death (by any cause in the absence of disease progression). Disease response was assessed according to Investigator assessment using modified Lugano criteria (Lugano 2014).	From first documented response until date of first documented disease progression or death from any cause, or data cut-off or end of study (whichever came first, assessed up to 2 years 5 months)
Part A (Dose Escalation): Duration of Complete Response (DoCR)	The anti-tumor activity of sabestomig in participants with r/r cHL was assessed. The DoCR was defined as the time from first documented CR, as per modified Lugano criteria (Lugano 2014) as assessed by the Investigator, until the date of first documented relapse/progression or death due to any cause (in the absence of disease progression). Disease response was assessed according to Investigator assessment using modified Lugano criteria (Lugano 2014).	From first documented complete response until date of first documented disease progression or death from any cause, or data cut-off or end of study (whichever came first, assessed up to 2 years 5 months)
Part A (Dose Escalation): Progression-free Survival (PFS)	The anti-tumor activity of sabestomig in participants with r/r cHL was assessed. PFS was defined as the time from first dose until the earlier of the date of first documented disease progression, as per modified Lugano criteria (Lugano 2014) as assessed by the Investigator, or death (by any cause in the absence of disease progression or subsequent anticancer treatment). Disease response was assessed according to Investigator assessment using modified Lugano criteria (Lugano 2014).	From start of treatment [C1D1 (each cycle was 28 days)] until date of first documented disease progression or data cut-off or end of study (whichever came first, assessed up to 2 years 5 months)
Part A (Dose Escalation): Overall Survival (OS)	The anti-tumor activity of sabestomig in participants with r/r cHL was assessed. The OS was defined as the time from the start of treatment until death due to any cause regardless of whether participant withdraws from treatment or receives another anti-lymphoma therapy.	From start of treatment [C1D1 (each cycle was 28 days)] until date of death due to any cause or data cut-off or end of study (whichever came first, assessed up to 2 years 5 months)
Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum	The presence of ADA for sabestomig in treated participants with r/r cHL was assessed.	On C1D1, C2D1, and until end of study [up to 2 years 5 months (each cycle was 28 days)]
Part A (Dose Escalation): Maximum Observed Concentration (Cmax)	The Cmax of sabestomig in participants with r/r cHL was assessed.	From C1D1 [before start of infusion (SOI) and at end of infusion (EOI)] to end of study [up to 2 years 5 months (each cycle was 28 days)]
Part A (Dose Escalation): Area Under the Concentration-time Curve (AUC)	The AUC of sabestomig in participants with r/r cHL was assessed.	From C1D1 (before SOI and at EOI) to end of study [up to 2 years 5 months (each cycle was 28 days)]
Part A (Dose Escalation): Clearance (CL)	The CL of sabestomig in participants with r/r cHL was assessed.	From C1D1 (before SOI and at EOI) to end of study [up to 2 years 5 months (each cycle was 28 days)]
Part A (Dose Escalation): Terminal Elimination Half-life (t½λz)	The t½λz of sabestomig in participants with r/r cHL was assessed.	From C1D1 (before SOI and at EOI) to end of study [up to 2 years 5 months (each cycle was 28 days)]
Part B (Dose Expansion): Duration of Response (DoR)	The DoR of sabestomig in participants with r/r cHL was planned to be assessed.	Up to approximately 2 years 90 days
Part B (Dose Expansion): Duration of Complete Response (DoCR)	The DoCR of sabestomig in participants with r/r cHL was planned to be assessed.	Up to approximately 2 years 90 days
Part B (Dose Expansion): Progression-free Survival (PFS)	The anti-tumor activity of sabestomig in participants with r/r cHL was planned to be assessed.	Up to approximately 2 years 90 days
Part B (Dose Expansion): Overall Survival (OS)	The anti-tumor activity of sabestomig in participants with r/r cHL was planned to be assessed.	Up to approximately 2 years 90 days
Part B (Dose Expansion): Number of Participants With Positive ADA Against Sabestomig in Serum	The presence of ADA for sabestomig in treated participants with r/r cHL was planned to be assessed.	Up to approximately 2 years 90 days
Part B (Dose Expansion): Maximum Observed Concentration (Cmax)	The Cmax of sabestomig in participants with r/r cHL was planned to be assessed.	Up to approximately 2 years 90 days
Part B (Dose Expansion): Area Under the Concentration-time Curve (AUC)	The AUC of sabestomig in participants with r/r cHL was planned to be assessed.	Up to approximately 2 years 90 days
Part B (Dose Expansion): Terminal Elimination Half-life (t½λz)	The t½λz of sabestomig in participants with r/r cHL was planned to be assessed.	Up to approximately 2 years 90 days
Part B (Dose Expansion): Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)	Proportion of participants reporting different levels of presence/magnitude/interference (as applicable) of diarrhea, rash, and fatigue over time based on PRO-CTCAE was planned to be evaluated. PRO-CTCAE was a PRO measurement system developed to evaluate symptomatic toxicity in participants on cancer clinical trials. The PRO-CTCAE Item Library included 124 items representing 78 symptomatic toxicities drawn from the CTCAE. PRO-CTCAE items were planned to evaluate the symptom attributes of frequency, severity, interference, amount, presence/absence. Each symptomatic AE was planned to be assessed by 1 to 3 attributes. Conditional branching logic was planned to be used with electronic data capture, thereby reducing respondent burden. The recall period was planned as the past 7 days and PRO-CTCAE responses were planned to score from 0 to 4 (or 0/1 for absent/present).	Up to approximately 2 years 90 days
Part B (Dose Expansion): Pediatric Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (Peds-PRO-CTCAE)	Proportion of participants reporting different levels of presence/magnitude/interference (as applicable) of diarrhea, rash, and fatigue over time based on peds-PRO-CTCAE was planned to be evaluated. The pediatric module included 130 items representing 62 symptomatic toxicities and permitted self-reporting by children and adolescents aged 7 to 17 years. In this study, 17 symptomatic toxicities were planned for selection. Thus, the total number of questions that participants would have answered ranged from 17 (assuming that no branching questions were triggered, ie, the participant answered '0' to the initial question for each symptom) to 42 items (assuming that all possible branching questions were triggered for every symptom posed to the participant).	Up to approximately 2 years 90 days
Part B (Dose Expansion): Patient Global Impression of Treatment Tolerability (PGI-TT)	Proportion of participants reporting different levels of overall side-effect bother over time based on the PGI-TT was planned to be evaluated. For adult participants only, the PGI-TT item was included to assess how a participant perceived the overall burden of treatment-related side effects of cancer treatment over the past 7 days. Participants were planned to be asked to choose the response that best described the level of burden by the side effect of their cancer treatment over the past week. The planned response options were:"not at all", "a little bit", "somewhat", "quite a bit", and "very much".	Up to approximately 2 years 90 days
Part B (Dose Expansion): European Organization for Research and Treatment of Cancer (EORTC) Item List (IL)XX QL2 [2-item Global Health-related Quality of Life (HRQoL)]	Proportion of participants reporting different levels of quality of life/health over time based on the European Organization for Research and Treatment of Cancer Item List (EORTC) ILXX QL2 items was planned to be evaluated. EORTC QLQ-C30 was a 30-item self-administered questionnaire designed for all cancer types. Questions were grouped into 5 multi-item functional scales (physical, role, emotional, cognitive, and social), 3 multi-item symptom scales (fatigue, pain, and nausea/vomiting), 2-item global HRQoL (QL2) scale, 5 single items assessing additional symptoms commonly reported by participants with cancer (dyspnea, loss of appetite, insomnia, constipation, and diarrhea), and 1 item on the financial impact of the disease. Participants were planned to answer QLQ-C30 questions in reference to how they had been over the past week. Final scores were planned to transform to range from 0 to 100, where higher scores indicated better functioning, better HRQoL, or greater level of symptoms.	Up to approximately 2 years 90 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A (Dose Escalation): Number of Participants With Adverse Events of Special Interest (AESIs)	The safety and tolerability of sabestomig in participants with r/r cHL were assessed. An AESI was an AE of scientific and medical interest specific to understanding of a study intervention and may have required close monitoring and rapid communication to AstraZeneca by the Investigator. The AESIs for sabestomig include events with a potential inflammatory or immune-mediated mechanism and which may require more frequent monitoring and/or interventions such as steroids, immunosuppressants and/or hormone replacement therapy.	From start of treatment [C1D1 (each cycle was 28 days)] up to 90 days post last dose (approximately 2 years 5 months)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel

Publications and helpful links

Helpful Links

• Redacted CSR synopsis
• Redacted SAP
• Redacted CSP

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2022
• Primary Completion (Actual): August 30, 2024
• Study Completion (Actual): September 4, 2025

Study Registration Dates

• First Submitted: January 19, 2022
• First Submitted That Met QC Criteria: January 19, 2022
• First Posted (Actual): February 1, 2022

Study Record Updates

• Last Update Posted (Estimated): October 2, 2025
• Last Update Submitted That Met QC Criteria: September 18, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Immunotherapy; Pharmacokinetics; Dose escalation; Bispecific antibody; Classical Hodgkin Lymphoma (cHL); Dose Expansion; r/r cHL; programmed cell death protein-1 (PD-1); Accelerated titration design (ATD); Modified toxicity probability interval-2 (mTPI-2); T cell immunoglobulin and mucin domain-containing protein-3 (TIM-3)
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Pathological Conditions, Signs and Symptoms; Recurrence
• Other Study ID Numbers: D9571C00001; 2021-003569-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No