A Phase I/II Study of AZD5863 in Adult Participants with Advanced or Metastatic Solid Tumors

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

Analytical,Diagnostic,Therapeutic Techniques and Equipment [E]-Surgical Procedures, Operative [E04], Diseases [C] - Neoplasms [C04]

Trial duration

6 Sep 2024 → ongoing

Decision date (initial)

2024-01-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

Dose Escalation
(1) To investigate the safety and tolerability, characterise DLTs and determine MTD and/or RP2D(s) of AZD5863 as a monotherapy or in combination in participants with advanced or metastatic solid tumors with CLDN18.2 expression
Dose Expansion
(1) To investigate the safety and tolerability of AZD5863 monotherapy or in combination in participants with advanced or metastatic solid tumors with CLDN18.2 expression
(2) To evaluate the preliminary antitumour activity of AZD5863 monotherapy or in combination in participants with advanced or metastatic solid tumors with CLDN18.2 expression

Secondary objectives 4

1. Dose Escalation and Dose Expansion: To evaluate the preliminary antitumor activity of AZD5863 monotherapy or in combination in participants with advanced or metastatic solid tumors with CLD18.2 expression
2. Dose Escalation and Dose Expansion: To characterize the PK of AZD5863 monotherapy or in combination in participants with advanced or metastatic solid tumors with CLD18.2 expression
3. Dose Escalation and Dose Expansion: To determine the immunogenicity of AZD5863 monotherapy or in combination in participants with advanced or metastatic solid tumors with CLD18.2 expression
4. Dose Escalation and Dose Expansion: To assess the preliminary antitumour activity of AZD5863 with target expression pre- and post-delivery of AZD5863 monotherapy or in combination

Conditions and MedDRA coding

Advanced or metastatic solid tumors

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Age ≥ 18 at the time of signing the informed consent
2. Histologically confirmed diagnosis of adenocarcinoma of the stomach, gastro-esophageal junction, esophagus, or pancreas
3. Must have at least one measurable lesion according to RECIST v1.1
4. Must show positive CLDN18.2 expression in tumor cells as determined by central IHC
5. Eastern Cooperative Oncology Group Performance status (ECOG PS): 0-1 at screening
6. Predicted life expectancy of ≥ 12 weeks
7. Adequate organ and bone marrow function measured within 28 days prior to first dose as defined by the protocol
8. Contraceptive use by men or women should be consistent with local regulations, as defined by the protocol
9. Must have received at least one prior line of systemic therapy in the advanced/metastatic setting

Exclusion criteria 10

1. Unresolved toxicity from prior anticancer therapy of Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 2 except for those defined by the protocol
2. Participant experienced unacceptable CRS or ICANS following prior TCE or CAR-T cell therapy
3. Active or prior documented autoimmune or inflammatory disorders within 3 years of start of treatment
4. CNS metastases or CNS pathology, as defined by the protocol, within 3 months prior to consent
5. Infectious disease including active HIV, active hepatitis B/C, uncontrolled infection with EBV, uncontrolled active systemic fungal, bacterial or other infection
6. Cardiac conditions as defined by the protocol
7. History of thromboembolic event within the past 3 months prior to the scheduled first dose of study intervention
8. Participant requires chronic immunosuppressive therapy
9. Participants on anticoagulation therapy with long-acting anticoagulants or other class of anticoagulants at therapeutic doses
10. Previous history of hemophagocytic lymphohistiocytosis (HLH) / macrophage activation syndrome (MAS)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

1. Dose Escalation: Incidence of AEs, AESIs, DLTs and SAEs
2. Dose Escalation: AEs leading to discontinuation of AZD5863
3. Dose Escalation: Assess clinically significant alterations in vital signs and abnormal laboratory parameters
4. Dose Expansion: Incidence of AEs, AESIs and SAEs
5. Dose Expansion: AEs leading to discontinuation of AZD5863
6. Dose Expansion: Assess clinically significant alterations in vital signs and abnormal laboratory parameters
7. Dose Expansion: According to RECIST v1.1: ORR

Secondary endpoints 7

1. Dose Escalation: According to RECIST v1.1: ORR
2. Dose Escalation and Dose Expansion: According to RECIST v1.1: DCR, DoR, PFS
3. Dose Escalation and Dose Expansion: Overall Survival
4. Dose Escalation and Dose Expansion: Serum concentrations of AZD5863
5. Dose Escalation and Dose Expansion: Serum PK parameters of AZD5863, including but not limited to Cmax, AUC, clearance and t1/2, as data allow
6. Dose Escalation and Dose Expansion: The number and percentage of participants who develop ADAs measured in serum
7. Dose Escalation and Dose Expansion: To investigate CLDN18.2 expression in tumour cells in relation to response to AZD5863

Investigational products

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

Test 1

Auxiliary 3

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

2 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

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

Documents 20 files

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

Application history

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