A Study to Assess the Safety and Efficacy of AZD7789 in Participants With Advanced or Metastatic Solid Cancer

NCT04931654 | Active Not Recruiting Phase 1 FDA Drug

• 4 other identifiers: D9570C000011529702022-502774-172021-000036-57
• Study Type: interventional
• Target: 136
• Locations: 10 countries
• Sites: 21

Brief Summary

This is a Phase I/IIa study designed to evaluate if experimental anti-PD-1 and anti-TIM-3 bispecific antibody, AZD7789 is safe, tolerable and efficacious in participants with advanced solid tumors.

Conditions

Carcinoma, Non-Small-Cell Lung; Gastric Cancer; Gastroesophageal Junction Cancer

Keywords

Solid tumor; Non-small cell lung cancer; NSCLC; Gastric Cancer; Gastroesophageal Junction Cancer; anti-PD-1/PD-L1; anti-TIM-3

Outcome Measures

Primary Outcomes (3)

• Number of participants with adverse events (AE), serious adverse events (SAE) and immune-mediated AEs (imAE)

  Number of participants with AEs, SAEs, imAEs including AEs leading to discontinuation of study intervention and clinically significant alterations in vital signs, laboratory parameters and ECG results

  From time of Informed Consent to 90 days post last dose of study intervention

• Number of participants with dose-limiting toxicity (DLT), as defined in the protoocol

  A DLT is a toxicity defined by the study protocol that occurs from the first dose of study intervention up to the end of the DLT evaluation period that is assessed as clearly unrelated to the primary disease or intercurrent illness.

  From the first patient until the end of the dose escalation period; approximately 18 months.

• Preliminary anti-tumour activity of AZD7789

  Objective response rate as defined by RECIST v1.1

  From first participant until last participant assessment; a duration of approximately 4 years. Disease assessments will be performed until progression or initiation of another anticancer therapy.

Secondary Outcomes (11)

• Objective response rate

  From first participant until last participant assessment; a duration of approximately 4 years. Disease assessments will be performed until progression or initiation of another anticancer therapy.

• Disease control rate

  From first documented response to confirmed progressive disease or death; approximate duration of 4 years.

• Duration of response

  From first documented response to confirmed progressive disease or death; approximate duration of 4 years.

• Progression-free survival

  From first dose of study intervention to confirmed progressive disease or death; approximate duration of 4 years.

• Overall survival

  From first dose of study intervention to death. Overall survival will be monitored for the duration of the study, which will last approximately 4 years.

Study Arms (6)

Dose Escalation Part A: NSCLC Immuno-oncology (IO) acquired or primary resistance

EXPERIMENTAL

AZD7789 monotherapy

Drug: AZD7789

Dose Expansion Part B1: NSCLC IO acquired resistance - RP2D level 1

EXPERIMENTAL

AZD7789 Monotherapy

Drug: AZD7789

Dose Expansion Part B2: NSCLC IO naive, PD-L1 50% or greater - RP2D level 1

EXPERIMENTAL

AZD7789 Monotherapy

Drug: AZD7789

Dose Expansion Part B3: NSCLC IO acquired resistance - RP2D level 2

EXPERIMENTAL

AZD7789 Monotherapy

Drug: AZD7789

Dose Expansion Part B4: advanced or metastatic gastric and GEJC IO acquired resistance- RP2D level 1

EXPERIMENTAL

AZD7789 monotherapy

Drug: AZD7789

Dose Expansion Part B5: NSCLC IO naive, PD-L1 1-49% - RP2D Level 1

EXPERIMENTAL

AZD7789 monotherapy

Drug: AZD7789

Interventions

AZD7789 DRUG

anti-PD-1 and anti-TIM-3 bispecific antibody

Dose Escalation Part A: NSCLC Immuno-oncology (IO) acquired or primary resistance; Dose Expansion Part B1: NSCLC IO acquired resistance - RP2D level 1; Dose Expansion Part B2: NSCLC IO naive, PD-L1 50% or greater - RP2D level 1; Dose Expansion Part B3: NSCLC IO acquired resistance - RP2D level 2; Dose Expansion Part B4: advanced or metastatic gastric and GEJC IO acquired resistance- RP2D level 1; Dose Expansion Part B5: NSCLC IO naive, PD-L1 1-49% - RP2D Level 1

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be ≥ 18 years of age
• Part A Dose-escalation cohorts and Part B Dose-expansion cohorts B1, B2, B3 and B5: Histologically or cytologically documented Stage IIIB to IV non-small cell lung carcinoma (NSCLC) not amenable to curative surgery or radiation.
• Part B Dose-expansion cohort B4: Histologically or cytologically documented advanced or metastatic gastric and gastro-esophageal junction adenocarcinoma (GEJC) not amenable to curative surgery or radiation.
• Must have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Provision of archival or fresh tumor tissue sample and/or consent to undergo mandatory on-treatment biopsy for participants enrolled in Part A Dose-escalation
• Provision of archival tumor tissue sample or fresh tissue sample for Part B Dose-expansion cohorts B1, B2, B3 and B5. Provision of fresh tumor tissue sample and consent to undergo mandatory on-treatment biopsy for cohort B4.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Non-pregnant women and willingness of female participants to avoid pregnancy or male participants willing to avoid fathering children through highly effective methods of contraception
• Adequate organ and bone marrow function measured within 28 days prior to first dose
• May have squamous or non-squamous NSCLC
• Must have received at least one prior line of systemic therapy, of which at least one prior line of therapy contained approved anti-PD-1/PD-L1
• Must have had immune-oncology (IO) acquired or primary resistance
• PD-L1 expression \< 1% or ≥ 1% documented
• May have squamous or non-squamous NSCLC
• Must have received at least one prior line of systemic therapy, of which only one prior line of therapy contained approved anti-PD-1/PD-L1

You may not qualify if:

• Patients with sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusions. Documented test result is mandatory for participants with non-squamous NSCLC histology. For participants with squamous NSCLC histology, testing is mandatory only if the participant is a never-smoker or in the presence of a mixed histology.
• Documented test result for any other known genomic alteration for which a targeted first line therapy is approved per local standard of care (SoC)
• Part B Dose-expansion Cohort B4: documented HER2 amplification (unless a SoC including an anti-HER2 therapy has been received); testing is not mandatory if not required per local guidelines.
• Unresolved toxicities of ≥ Grade 2 from prior therapy
• Any prior ≥ Grade 3 immune-mediated adverse event (imAE) while receiving immunotherapy or any unresolved imAE ≥ Grade 2
• Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy
• Symptomatic central nervous system (CNS) metastasis or leptomeningeal disease
• History of symptomatic and objectively confirmed arterial (including myocardial infarction) or venous thromboembolic event within 6 months prior to the first dose of study intervention, unless participant is on treatment with adequate antithrombotic medication and is considered to be stable by the Investigator.
• History of organ transplant or allogenic haematopoietic stem cell transplant
• History of clinically significant arrythmia as judged by the Investigator
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, cardiomyopathy of any etiology, symptomatic congestive heart failure, uncontrolled hypertension, uncontrolled diabetes mellitus, unstable angina pectoris, history of myocardial infarction within the past 6 months, serious chronic gastrointestinal conditions associated with diarrhea, active non infectious skin disease. Part B Dose-expansion Cohort B4, medication-resistant ascites requiring drainage in the last 28 days prior the start of AZD7789 and/or the occurrence of active gastro-intestinal bleeding, as judged by the Investigator.
• Active or prior documented autoimmune or inflammatory disorders, including inflammatory bowel disease (eg, colitis or Crohn's disease), diverticulitis (with the exception of diverticulosis), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.. Some exceptions have been specified in the protocol
• Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD
• Major surgical procedure within 28 days prior to the first dose of study intervention or still recovering from prior surgery
• Other invasive malignancy within 2 years prior to screening

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (21)

Research Site

Atlanta, Georgia, 30322, United States

Location

Research Site

Fort Wayne, Indiana, 46804, United States

Location

Research Site

New York, New York, 10029, United States

Location

Research Site

Nashville, Tennessee, 37203, United States

Location

Research Site

Toronto, Ontario, M5G 2M9, Canada

Location

Research Site

Beijing, 100142, China

Location

Research Site

Guangzhou, 510060, China

Location

Research Site

Bordeaux, 33076, France

Location

Research Site

Rennes, 35000, France

Location

Research Site

Villejuif, 94805, France

Location

Research Site

Tbilisi, 0112, Georgia

Location

Research Site

Chūōku, 104-0045, Japan

Location

Research Site

Kashiwa, 277-8577, Japan

Location

Research Site

Chisinau, MD-2025, Moldova

Location

Research Site

Amsterdam, 1066 CX, Netherlands

Location

Research Site

Barcelona, 08035, Spain

Location

Research Site

Madrid, 28027, Spain

Location

Research Site

Ankara, 06010, Turkey (Türkiye)

Location

Research Site

Ankara, 06200, Turkey (Türkiye)

Location

Research Site

Ankara, 06800, Turkey (Türkiye)

Location

Research Site

Karşıyaka, 35575, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Stomach Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a FTIH, multicenter, open-label, dose-escalation and dose-expansion study. The study includes 2 parts: Part A Dose Escalation and Part B Dose Expansion. Initially, participants with Stage IIIB to IV NSCLC will be enrolled in the study; additional tumor types may be explored and added in a future amendment to the CSP.

Study Record Dates

• First Submitted: May 26, 2021
• First Posted: June 18, 2021
• Study Start: September 28, 2021
• Primary Completion: December 4, 2024
• Study Completion (Estimated): August 12, 2026
• Last Updated: October 9, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified 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.

Locations

FR (3); ES (2); CA (1); US (4); NL (1); CN (2); JP (2); TU (4); MO (1); GE (1)