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 AZD7789 in patients with relapsed/refractory classical Hodgkin Lymphoma (r/r cHL).

Study Overview

• Status: Recruiting
• Conditions: Relapsed or Refractory Classical Hodgkin Lymphoma
• Intervention / Treatment: Drug: AZD7789

Detailed Description

This is a Phase I/II, open-label multi-center study will have AZD7789 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.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Recruiting
      • Research Site
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X6
      • Recruiting
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Recruiting
      • Research Site
• China
  • Beijing, China, 100036
    • Suspended
    • Research Site
  • Zhengzhou, China, 450008
    • Suspended
    • Research Site
• Denmark
  • København Ø, Denmark, 2100
    • Recruiting
    • Research Site
  • Odense, Denmark, 5000
    • Recruiting
    • Research Site
• France
  • Lille Cedex, France, 59037
    • Recruiting
    • Research Site
  • Paris, France, 75010
    • Suspended
    • Research Site
  • Villejuif, France, 94805
    • Suspended
    • Research Site
• Germany
  • Köln, Germany, 50924
    • Withdrawn
    • Research Site
• Italy
  • Bologna, Italy, 40138
    • Recruiting
    • Research Site
  • Milan, Italy, 20141
    • Suspended
    • Research Site
  • Napoli, Italy, 80131
    • Recruiting
    • Research Site
• Spain
  • Barcelona, Spain, 8035
    • Recruiting
    • Research Site
  • Valencia, Spain, 46010
    • Recruiting
    • Research Site
• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • Recruiting
    • Research Site
  • Oxford, United Kingdom, 0X3 7LJ
    • Recruiting
    • Research Site
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • Research Site
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Research Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Research Site
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • 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 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 CNS involvement or leptomeningeal disease.
• History of organ transplantation (e.g., stem cell or solid organ transplant).
• Any venous or arterial thromboembolic event within ≤ 6 months prior to the first dose of study intervention.
• Active infection including TB, 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 uncontrolled 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 AZD7789.	Drug: AZD7789; Patients will receive AZD7789 (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 AZD7789 once the recommended phase 2 dose (RP2D) has been determined.	Drug: AZD7789; Patients will receive AZD7789 (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 AZD7789 once the RP2D has been determined.	Drug: AZD7789; Patients will receive AZD7789 (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 incidence of adverse events (AEs)	To assess safety and tolerability of AZD7789 in patients with r/r cHL.	Approximately up to 2 years 90 days
Part A (Dose Escalation): Number of patients with dose-limiting toxicities (DLTs)	To determine the maximum tolerated dose (MTD). To determine the incidence of DLT.	From first dose until 28 days from the last patient first dose [within 28 days DLT period]
Part B (Dose Expansion): Cohort B1: Objective response rate (ORR)	To assess anti-tumor activity of AZD7789 in patients with r/r cHL. ORR defined as CR + PR as per modified Lugano criteria (Lugano 2014).	Up to 2 years of treatment
Part B (Dose Expansion): Cohort B2: Complete response rate (CRR)	To assess anti-tumor activity of AZD7789 in patients with r/r cHL. CRR is defined as CR as per modified Lugano criteria (Lugano 2014).	Up to 2 years of treatment
Part B (Dose Expansion): Number of incidence of adverse events (AEs)	To assess safety and tolerability of AZD7789 in patients with r/r cHL.	Approximately up to 2 years 90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A (Dose Escalation): Complete Response Rate (CRR)	To assess anti-tumor activity of AZD7789 in patients with r/r cHL. CRR is defined as CR as per modified Lugano criteria (Lugano 2014).	Up to 2 years of treatment
Part A (Dose Escalation): Objective Response Rate (ORR)	To assess anti-tumor activity of AZD7789 in patients with r/r cHL. ORR defined as CR + PR as per modified Lugano criteria (Lugano 2014).	Up to 2 years of treatment
Part A (Dose Escalation): Duration of Response (DoR)	To assess DoR of AZD7789 in patients with r/r cHL.	Up to approximately 5 years
Part A (Dose Escalation): Duration of Complete Response (DoCR)	To assess DoCR of AZD7789 in patients with r/r cHL	Up to approximately 5 years
Part A (Dose Escalation): Progression-free Survival (PFS)	To assess anti-tumor activity of AZD7789 in patients with r/r cHL.	Up to approximately 5 years
Part A (Dose Escalation): Overall Survival (OS)	To assess anti-tumor activity of AZD7789 in patients with r/r cHL.	Up to approximately 5 years
Part A (Dose Escalation): Number of patients with positive anti-drug antibodies against AZD7789 in serum	To assess the presence of anti-drug antibodies for AZD7789 in treated patients with r/r cHL.	Up to 2 years
Part A (Dose Escalation): Maximum observed concentration (Cmax)	To assess the Cmax of AZD7789 in patients with r/r cHL.	Up to 2 years
Part A (Dose Escalation): Area under the concentration-time curve (AUC)	To assess AUC of AZD7789 in patients with r/r cHL.	Up to 2 years
Part A (Dose Escalation): Terminal elimination half-life (t½)	To assess t½ of AZD7789 in patients with r/r cHL.	Up to 2 years
Part B (Dose Expansion): Duration of Response (DoR)	To assess DoR of AZD7789 in patients with r/r cHL.	Up to approximately 5 years
Part B (Dose Expansion): Duration of Complete Response (DoCR)	To assess DoCR of AZD7789 in patients with r/r cHL	Up to approximately 5 years
Part B (Dose Expansion): Progression-free Survival (PFS)	To assess anti-tumor activity of AZD7789 in patients with r/r cHL.	Up to approximately 5 years
Part B (Dose Expansion): Overall Survival (OS)	To assess anti-tumor activity of AZD7789 in patients with r/r cHL.	Up to approximately 5 years
Part B (Dose Expansion): Number of patients with positive anti-drug antibodies against AZD7789 in serum	To assess the presence of anti-drug antibodies for AZD7789 in treated patients with r/r cHL.	Up to 2 years
Part B (Dose Expansion): Maximum observed concentration (Cmax)	To assess the Cmax of AZD7789 in patients with r/r cHL.	Up to 2 years
Part B (Dose Expansion): Area under the concentration-time curve (AUC)	To assess AUC of AZD7789 in patients with r/r cHL.	Up to 2 years
Part B (Dose Expansion): Terminal elimination half-life (t½)	To assess t½ of AZD7789 in patients with r/r cHL.	Up to 2 years
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 will be evaluated.	Up to 2 years of treatment
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 will be evaluated.	Up to 2 years of treatment
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.	Up to 2 years of treatment
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 will be evaluated.	Up to 2 years of treatment

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2022
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): October 15, 2027

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 (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

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); T cell immunoglobulin and mucin domain-containing protein-3(TIM-3); Modified toxicity probability interval-2 (mTPI-2)
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease
• 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 de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• 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