A Phase I/IIa Open-label Dose Escalation and Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of AZD7789, an anti-PD-1 and anti-TIM-3 Bispecific Antibody, in Participants with Advanced or Metastatic Solid Tumors

AstraZeneca AB7 sites in 3 countries95 target enrollmentMay 31, 2024

Overview

Phase: Phase 1/2
Intervention: Not specified
Conditions: Not specified
Sponsor: AstraZeneca AB
Enrollment: 95
Locations: 7
Primary Endpoint: Adverse Events (AEs), imAEs, Serious Adverse Events (SAEs), and DLTs
Status: Active, not recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

For Part A Dose Escalation: To assess the safety and tolerability, characterize the Dose Limiting Toxicities (DLTs), and determine the Maximum Tolerated Dose (MTD) or Optimal Biological Dose (OBD) and Recommended Phase 2 Dose (RP2D or multiple doses for evaluation for RP2D) of AZD7789 in participants with advanced or metastatic solid tumors.

For Part B Dose Expansion: To assess the safety, tolerability and preliminary antitumor activity of AZD7789 in participants with advanced or metastatic solid tumors

Registry

euclinicaltrials.eu

Start Date

May 31, 2024

End Date

TBD

Last Updated

last year

Investigators

Sponsor

AstraZeneca AB

Responsible Party

Principal Investigator

AstraZeneca Clinical Study Information Center

Scientific

AstraZeneca AB

Eligibility Criteria

Inclusion Criteria

•Must be ≥ 18 years of age
•Adequate organ and bone marrow function measured within 28 days prior to first dose
•Part A Dose Escalation Additional Inclusion Criteria: • 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
•Part B Dose Expansion Cohort B1 and B3 Additional Inclusion Criteria: • 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 • Must have had IO acquired resistance • PD- L1 expression ≥ 1% documented
•Part B Dose Expansion Cohort B2 and B5 Additional Inclusion Criteria: • May have squamous or non-squamous NSCLC • Must not have received any prior Immunotherapy, but may have received a maximum of one prior treatment for NSCLC consisting of standard of care platinum-based chemotherapy only. • Cohort B2: PD-L1 expression ≥ 50% documented • Cohort B5: PD-L1 expression 1-49% documented
•Part B Dose Expansion Cohort B4 Additional Inclusion Criteria: • Must have received at least one but no more than two prior lines of systemic therapy in the advanced/metastatic setting, of which only one prior line of therapy contained an approved anti-PD-1/PD-L1 therapy • Must have had IO acquired resistance • There are no PD-L1 status requirements for this cohort.
•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 or gastro-esophageal junction (GEJ) adenocarcinoma 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 fresh tumor tissue sample at screening and on treatment (mandatory sample in Part A pharmacodynamic backfill cohorts and cohort B

Exclusion Criteria

•Participants with any of the following: (a) Sensitizing EGFR mutations or ALK fusions (documented test result 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). (b) Documented test result for any other known genomic alteration for which a targeted therapy is approved in 1L per local SoC (such as ROS1, NTRK fusions, BRAF, V600E mutation, etc); testing is not mandatory if not required per local guidelines. (c) 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.
•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. For 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
•Radiotherapy treatment to the lung within ≤ 4 weeks of the first dose of AZD
•Palliative bone radiotherapy is allowed if ≥ 2 weeks prior to the first dose of AZD
•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
•Any previous treatment with anti-TIM-3 therapy in any setting is not permitted. For Part A, Cohorts B1 and B3: treatment with investigational therapy prior to initiation of study treatment except where the most recent line of therapy was investigational agents added to approved anti-PD-1/PD-L1 as part of standard care. Investigational agents may be given as prior lines of therapy (other than the most recent line) and as monotherapy. Where investigational agents are the most recent line of therapy, they must be given in combination with approved anti-PD-1/PD-L

Outcomes

Primary Outcomes

Adverse Events (AEs), imAEs, Serious Adverse Events (SAEs), and DLTs

AEs leading to discontinuation of AZD7789

Clinically significant alterations in vital signs, laboratory parameters, and ECG results

Part B Dose Expansion: Objective Response Rate (ORR) according to RECIST v1.1

Secondary Outcomes

For Dose Escalation: o ORR, Disease Control Rate (DCR), Duration of Response (DoR), and Progression-free Survival (PFS) according to RECIST v1.1, changes in ctDNA and Overall Survival (OS)
For Dose Expansion: o DCR, DoR, PFS according to RECIST v1.1, changes in ctDNA and OS
For Dose Escalation and Expansion: o PK parameters including Cmax, AUC, clearance, and t 1/2
For Dose Escalation and Expansion: o Incidence of ADAs against AZD7789 in serum