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

Sponsor
AstraZeneca (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04931654
Collaborator
(none)
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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

Study Type:
Interventional
Anticipated Enrollment :
81 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
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.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.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Sep 28, 2021
Anticipated Primary Completion Date :
Jan 23, 2025
Anticipated Study Completion Date :
Jul 1, 2025

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

  1. 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

  2. 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.

  3. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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).

  8. 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.

  9. 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.

  10. 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.

  11. 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

Ages Eligible for Study:
18 Years to 130 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Must be ≥ 18 years of age

  • Histologically or cytologically documented Stage IIIB to IV non-small cell lung carcinoma (NSCLC) 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 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 or primary resistance

  • PD-L1 expression < 1% or ≥ 1% documented

Part B Dose Expansion Cohort B1 Additional Inclusion Criteria:
  • May have squamous or non-squamous NSCLC

  • 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

  • Must have had IO acquired resistance

  • PD- L1 TPS ≥ 1% 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 TPS ≥ 50% documented

Exclusion Criteria:
  • 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)

  • 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

  • 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 arrhythmia which is symptomatic or requires treatment; symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia

  • 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

  • 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

  • Previous treatment with anti-TIM-3 therapy in any setting

  • Current or prior use of immunosuppressive medication within 14 days prior to the first dose of study intervention

  • Any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for noncancer-related conditions is acceptable.

  • 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

  • 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.
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT04931654
Other Study ID Numbers:
  • D9570C00001
  • 2021-000036-57
  • 152970
First Posted:
Jun 18, 2021
Last Update Posted:
Aug 9, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by AstraZeneca
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 9, 2022