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
- Advanced or Metastatic Solid Tumors
- Registration Number
- JPRN-jRCT2031220675
- Lead Sponsor
- Hibi Kazushige
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 24
Must be 18 or more years of age
- Japan mini dose escalation phase: Histological or cytological confirmation of a solid, malignant tumor refractory to standard therapies or for which no standard therapies exist (Recruiting of Japan mini dose escalation phase has ended).
- Part B Dose Expansion cohorts B2 and B3: Histologically or cytologically documented Stage IIIB to IV non-small cell lung carcinoma (NSCLC) not amenable to curative surgery or radiation (Recruiting of cohort B3 has ended).
- Must have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- Provision of archival tumor tissue sample or fresh tissue sample for Part B Dose-expansion cohorts B2 and B3. 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
- Part B Dose Expansion Cohort 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% or more documented
- 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% or more 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, of which only one prior line of therapy contained an approved anti-PD-1/PD-L1
- Must have had IO acquired resistance
- There are no PD-L1 status requirements for this cohort
- Part B Dose Expansion: 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. (not applicable for the Japan mini dose escalation phase)
- Part B Dose Expansion: Documented test result for any other known genomic alteration for which a targeted first line therapy is approved per local standard of care (SoC) (not applicable for the Japan mini dose escalation phase)
- 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 or more from prior therapy
- Any prior Grade 3 or more immune-mediated adverse event (imAE) while receiving immunotherapy or any unresolved imAE Grade 2 or more
- 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
- 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 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
- 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 tr
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method - Adverse events (AEs), immune-mediated adverse events (imAEs), serious adverse events (SAEs), and dose limiting toxicities (DLTs)<br><br>- AEs leading to discontinuation of AZD7789<br><br>- Clinically significant alterations in vital signs, laboratory parameters, and electrocardiogram (ECG) results
- Secondary Outcome Measures
Name Time Method