A Study to Assess the Safety and Efficacy of AZD7789 in Participants With Advanced or Metastatic Solid Cancer
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1/Phase 2 |
Detailed Description
This first time in patients, open-label, multi-centre study will have AZD7789 administered intravenously (IV) to participants with advanced solid tumors. This study will have 2 parts: Part A which will have dose escalation cohorts and Part B which will have the dose expansion cohorts.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Dose Escalation Part A: NSCLC Immuno-oncology (IO) acquired or primary resistance AZD7789 monotherapy |
Drug: AZD7789
anti-PD-1 and anti-TIM-3 bispecific antibody
|
Experimental: Dose Expansion Part B1: NSCLC IO acquired resistance AZD7789 Monotherapy |
Drug: AZD7789
anti-PD-1 and anti-TIM-3 bispecific antibody
|
Experimental: Dose Expansion Part B2: NSCLC IO naive AZD7789 Monotherapy |
Drug: AZD7789
anti-PD-1 and anti-TIM-3 bispecific antibody
|
Outcome Measures
Primary Outcome Measures
- Number of participants with adverse events (AE), serious adverse events (SAE) and immune-mediated AEs (imAE) [From time of Informed Consent to 90 days post last dose of study intervention]
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
- Number of participants with dose-limiting toxicity (DLT), as defined in the protoocol [From the first patient until the end of the dose escalation period; approximately 18 months.]
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.
- Preliminary anti-tumour activity of AZD7789 [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.]
Objective response rate as defined by RECIST v1.1
Secondary Outcome Measures
- 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.]
Objective response rate as defined by RECIST v1.1
- Disease control rate [From first documented response to confirmed progressive disease or death; approximate duration of 4 years.]
The percentage of participants according to RECIST v1.1 with a response or stable disease
- Duration of response [From first documented response to confirmed progressive disease or death; approximate duration of 4 years.]
The time from first response according to RECIST v1.1 until progression or death
- Progression-free survival [From first dose of study intervention to confirmed progressive disease or death; approximate duration of 4 years.]
The time from first dose of study intervention until the date of objective disease progression or death
- 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.]
The time from first dose of study intervention until death due to any cause
- Pharmacokinetics of AZD7789: Maximum plasma concentration of the study drug (Cmax) [From first dose of study intervention, at predefined intervals throughout the administration of study intervention; approximately 4 years.]
Maximum observed plasma concentration of the study drug.
- Immunogenicity of AZD7789 [From first dose of study intervention, at predefined intervals throughout the administration of study intervention. A duration of approximately 4 years.]
The number and percentage of participants who develop detectable anti-drug antibodies (ADA).
- Pharmacokinetics of AZD7789: Area Under the concentration-time curve (AUC) [From first dose of study intervention, at predefined intervals throughout the administration of study intervention; approximately 4 years.]
Area under the plasma concentration-time curve.
- Pharmacokinetics of AZD7789: Clearance [From first dose of study intervention, at predefined intervals throughout the administration of study intervention; approximately 4 years.]
A pharmacokinetic measurement of the volume of plasma from which the study drug is completely removed per unit time.
- Pharmacokinetics of AZD7789: Terminal elimination half-life (t 1/2) [From first dose of study intervention, at predefined intervals throughout the administration of study intervention; approximately 4 years.]
Terminal elimination half life.
- Preliminary anti-tumour activity of AZD7789: Changes in circulating tumor DNA (ctDNA) [From first dose of study intervention, at predefined intervals throughout the administration of study intervention; approximately 4 years.]
Changes in ctDNA between baseline and on treatment.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Must be ≥ 18 years of age
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Histologically or cytologically documented Stage IIIB to IV non-small cell lung carcinoma (NSCLC) not amenable to curative surgery or radiation
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Must have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
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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
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Provision of archival tumor tissue sample or fresh tissue sample for Part B Dose-expansion participants
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
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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
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Adequate organ and bone marrow function measured within 28 days prior to first dose
Part A Dose Escalation Additional Inclusion Criteria:
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May have squamous or non-squamous NSCLC
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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
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Must have had immune-oncology (IO) acquired or primary resistance
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PD-L1 expression < 1% or ≥ 1% documented
Part B Dose Expansion Cohort B1 Additional Inclusion Criteria:
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May have squamous or non-squamous NSCLC
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Must have received at least one but no more than 2 prior lines of systemic therapy, of which only one prior line of therapy contained approved anti-PD-1/PD-L1
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Must have had IO acquired resistance
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PD- L1 TPS ≥ 1% documented
Part B Dose Expansion Cohort B2 Additional Inclusion Criteria:
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May have squamous or non-squamous NSCLC
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Must not have received prior systemic therapy including IO therapy in the first-line setting
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PD-L1 TPS ≥ 50% documented
Exclusion Criteria:
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Patients with sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusions
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Documented test result for any other known genomic alteration for which a targeted first line therapy is approved per local standard of care (SoC)
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Unresolved toxicities of ≥ Grade 2 from prior therapy
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Any prior ≥ Grade 3 immune-mediated adverse event (imAE) while receiving immunotherapy or any unresolved imAE ≥ Grade 2
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Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy
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Symptomatic central nervous system (CNS) metastasis or leptomeningeal disease
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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
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History of organ transplant or allogenic haematopoietic stem cell transplant
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Infectious disease exclusions: Active infection including TB, HIV, hepatitis A, chronic or active hepatitis B, chronic or active hepatitis C, active COVID-19 infection
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History of arrhythmia which is symptomatic or requires treatment; symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia
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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
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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
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Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD
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Major surgical procedure within 28 days prior to the first dose of study intervention or still recovering from prior surgery
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Other invasive malignancy within 2 years prior to screening
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Congenital long QT syndrome or history of QT prolongation associated with other medications that cannot be changed or discontinued based on a cardiologist assessment
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Previous treatment with anti-TIM-3 therapy in any setting
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Current or prior use of immunosuppressive medication within 14 days prior to the first dose of study intervention
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Any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for noncancer-related conditions is acceptable.
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Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention. Note: Participants should not receive live vaccine while receiving study intervention and up to 30 days after the last dose of study intervention
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Radiotherapy treatment to the lung within ≤ 4 weeks of the first dose of AZD7789. Palliative bone radiotherapy is allowed if ≥ 2 weeks prior to the first dose of AZD7789.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Research Site | Atlanta | Georgia | United States | 30322 |
2 | Research Site | New York | New York | United States | 10029 |
3 | Research Site | Nashville | Tennessee | United States | 37203 |
4 | Research Site | Toronto | Ontario | Canada | M5G 2M9 |
5 | Research Site | Bordeaux | France | 33076 | |
6 | Research Site | Villejuif Cedex | France | 94805 | |
7 | Research Site | Amsterdam | Netherlands | 1066 CX | |
8 | Research Site | Barcelona | Spain | 08035 | |
9 | Research Site | Madrid | Spain | 28027 |
Sponsors and Collaborators
- AstraZeneca
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- D9570C00001
- 2021-000036-57
- 152970