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
- Conditions
- Maagdarmstelselneoplasmata benigneMetatstatic Solid TumorsSolid tumors10038666
- Registration Number
- NL-OMON56048
- Lead Sponsor
- Astra Zeneca
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 14
General Inclusion Criteria for all cohorts:
• Must be >= 18 years of age
• Part A, B1, B2 and B3: Histologically or cytologically documented Stage IIIB
to IV non-small cell lung carcinoma (NSCLC) not amenable to curative surgery or
radiation
• Part B4: Histologically or cytologically documented advanced or metastatic
gastric and GEJC not amendable to curative surgery
• Must have at least one measurable lesion according to Response Evaluation
Criteria in Solid Tumors (RECIST) v1.1
• Provision of fresh tumor tissue sample and consent to undergo mandatory
on-treatment biopsy for participants enrolled in Part A Dose-escalation
participants
• Provision of archival tumor tissue sample or fresh tissue sample for Part B
Dose-expansion participants
• 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.
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 resistance
• PD-L1 <1% of >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% as determined by IHC
Part B Dose Expansion Cohort B2 Additional Inclusion Criteria:
• May have squamous or non-squamous NSCLC
• Must not have received prior systemic therapy including IO therapy in the
first-line setting
• PD-L1 expression >= 50% as determined by IHC
Part B Dose Expansion Cohort B4 Additional Inclusion Criteria:
• Must not 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
• Patients with sensitizing epidermal growth factor receptor (EGFR) mutations
or anaplastic lymphoma kinase (ALK) fusions
• 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 an SoC
including an anti-HER2 therapy has been received)
• 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
study drug dosing, unless participant is on treatment with adequate
antithrombotic medication and is considered to be stable by the investigator.
• History of organ transplant or allogenic hematopoietic stem cell transplant.
• Infectious disease exclusions: Active infection including TB, HIV, hepatitis
A, chronic or active hepatitis B, chronic or active hepatitis C, active
COVID-19 infection
• History of clinically significant arrhythmia 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. For 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
• 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, 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 of care. Investigational agents
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method