A study to assess the safety and efficacy of AZD7789 in participants with advanced or metastatic solid cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

4 Oct 2021 → 27 Feb 2025

Decision date (initial)

2024-06-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2022-502774-17-00

EudraCT number

2021-000036-57

ClinicalTrials.gov

NCT04931654

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Pharmacokinetic, Efficacy, Pharmacogenomic, Safety, Pharmacodynamic, Therapy, Pharmacogenetic

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

Secondary objectives 4

1. For Part A Dose Escalation: To assess the preliminary antitumor activity of AZD7789 in participants with advanced or metastatic solid tumours.
2. For Part B Dose Expansion: To further assess the preliminary antitumor activity of AZD7789 in participants with advanced or metastatic solid tumours.
3. For both Part A Dose Escalation and Part B Dose Expansion: To assess the PK of AZD7789 in participants with advanced or metastatic solid tumours.
4. For both Part A Dose Escalation and Part B Dose Expansion: To assess the immunogenicity of AZD7789 in participants with advanced or metastatic solid tumours.

Conditions and MedDRA coding

Advanced or metastatic gastric and gastro-esophageal junction (GEJ) adenocarcinoma

Study design 4 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Must be ≥ 18 years of age
2. 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.
3. 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.
4. Must have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
5. Provision fresh tumor tissue sample at screening and on treatment (mandatory sample in Part A pharmacodynamic backfill cohorts and cohort B4. Optional in cohorts B1, B2, B3 and B5 providing archival tissue is available).
6. Provision of archival tumor tissue sample at screening if available.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
8. Predicted life expectancy of ≥ 12 weeks.
9. 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
10. Adequate organ and bone marrow function measured within 28 days prior to first dose
11. 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
12. 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
13. 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
14. 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.

Exclusion criteria 20

1. 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.
2. Unresolved toxicities of ≥ Grade 2 from prior therapy
3. Any prior ≥ Grade 3 immune-mediated adverse event (imAE) while receiving immunotherapy or any unresolved imAE ≥ Grade 2
4. Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy
5. Symptomatic central nervous system (CNS) metastasis or leptomeningeal disease
6. 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.
7. History of organ transplant or allogenic haematopoietic stem cell transplant
8. Infectious disease exclusions: Active infection including TB, HIV, active hepatitis A, chronic or active hepatitis B, chronic or active hepatitis C, active COVID-19 infection
9. History of clinically significant arrythmia as judged by the Investigator
10. 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.
11. 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
12. Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD
13. Major surgical procedure within 28 days prior to the first dose of study intervention or still recovering from prior surgery
14. 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.
15. Other invasive malignancy within 2 years prior to screening
16. Congenital long QT syndrome or history of QT prolongation associated with other medications that cannot be changed or discontinued based on a cardiologist assessment
17. 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-L1. For Part B Dose-expansion Cohort B4: investigational agents, other than investigational immune checkpoint inhibitors or other IO agents, may be given as any prior lines of therapy.
18. Current or prior use of immunosuppressive medication within 14 days prior to the first dose of study intervention
19. Any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for noncancer-related conditions is acceptable.
20. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Adverse Events (AEs), imAEs, Serious Adverse Events (SAEs), and DLTs
2. AEs leading to discontinuation of AZD7789
3. Clinically significant alterations in vital signs, laboratory parameters, and ECG results
4. Part B Dose Expansion: Objective Response Rate (ORR) according to RECIST v1.1

Secondary endpoints 4

1. 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)
2. For Dose Expansion: o DCR, DoR, PFS according to RECIST v1.1, changes in ctDNA and OS
3. For Dose Escalation and Expansion: o PK parameters including Cmax, AUC, clearance, and t 1/2
4. For Dose Escalation and Expansion: o Incidence of ADAs against AZD7789 in serum

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

3 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 34 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications