EVORPACEPT for Advanced HER2-overexpressing gastric adenocarcinoma | Advanced HER2-overexpressing gastroesophageal junction adenocarcinoma

Inclusion criteria

• {"criterion_text":"- Age ≥18 years (except in regions in which the minimum age for subject participation is >18 years)"}
• {"criterion_text":"- Patients with HER2-overexpressing advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma that has progressed on or after a prior HER2-directed agent and fluoropyrimidine- or platinum-containing chemotherapy (2nd-line or 3rd-line). Phase 2: HER2 overexpression determined by an FDA-approved test for gastric/GEJ cancer. If safe and feasible, it is recommended that patient eligibility be based on a biopsy obtained after prior trastuzumab treatment. Phase 3: HER2 overexpression determined by HER2 protein overexpression and/or HER2 gene amplification in tumor specimens assessed with FDA-approved (and local regulatory authority approved) tests specific for gastric cancer. (HER2 positivity will be centrally assessed for eligibility in Phase 3)"}
• {"criterion_text":"- Patients must have at least one measurable lesion as defined by RECIST version 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions"}
• {"criterion_text":"- Adequate bone marrow, renal, liver, cardiac (via ECG), clotting (INR/PT and PTT) function"}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) must be 0 or 1"}
• {"criterion_text":"- Resolved acute effects of any prior therapy"}
• {"criterion_text":"- Patients of childbearing potential must be non-pregnant and must agree to use a highly effective method of contraception throughout the study"}
• {"criterion_text":"- Consent to the study and study procedures"}

Exclusion criteria

• {"criterion_text":"- Patients with known symptomatic CNS metastases or leptomeningeal disease requiring steroids. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases and are clinically stable off anticonvulsants for at least 4 weeks and are neurologically stable before enrollment"}
• {"criterion_text":"- Prior radiotherapy within 2 weeks of start of study treatment. Note: Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease"}
• {"criterion_text":"- Prior treatment with anti-CD47 or anti-SIRPα agent or ramucirumab or any other systemic anticancer therapy within 4 weeks of starting study treatment"}
• {"criterion_text":"- Any Grade 3-4 GI bleeding or history of deep vein thrombosis (DVT), pulmonary embolism (PE), arterial thrombosis or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered \"significant\") within 3 months prior to first dose of Cycle 1 Day 1"}
• {"criterion_text":"- Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis"}
• {"criterion_text":"- Prior history of GI perforation/fistula (within 6 months of first dose of protocol therapy) or risk factors for perforation"}

Primary endpoints

• {"endpoint_text":"- Phase II: Objective response rate (ORR; CR or PR using the Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1 for solid tumors) based on investigator assessment. Dropouts will be analyzed as non-responders.","definition_or_measurement_approach":"ORR defined as CR or PR per RECIST v1.1 assessed by investigator; dropouts analysed as non-responders."}
• {"endpoint_text":"- Phase III: Overall survival (OS)","definition_or_measurement_approach":"Overall survival measured as time from randomization (or study entry) to death from any cause."}

Secondary endpoints

• {"endpoint_text":"- Phase II: Objective response rate (ORR; CR or PR using the Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1 for solid tumors) based on blinded independent central review (BICR).","definition_or_measurement_approach":"ORR per RECIST v1.1 assessed by blinded independent central review (BICR)."}
• {"endpoint_text":"- Phase II: Duration of response (DoR), disease control rate (DCR), time to tumor progression (TTP) based on investigator and BICR assessment.","definition_or_measurement_approach":"DoR, DCR, and TTP assessed by investigator and BICR per RECIST v1.1."}
• {"endpoint_text":"- Phase II: Progression-free survival (PFS) based on investigator and BICR assessment, and overall survival (OS).","definition_or_measurement_approach":"PFS assessed by investigator and BICR; OS measured as time to death."}
• {"endpoint_text":"- Phase II: Adverse Events as characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v. 5.0), timing, seriousness, and relationship to study therapy;","definition_or_measurement_approach":"Safety assessed by recording AEs graded per NCI CTCAE v5.0, including seriousness and relationship to study therapy."}
• {"endpoint_text":"- Phase II: Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v. 5.0) and timing.","definition_or_measurement_approach":"Laboratory abnormalities summarized by type, frequency, severity per NCI CTCAE v5.0 and timing."}
• {"endpoint_text":"- Phase II: Pharmacokinetic exposure of ALX148 such as trough (pre-infusion) and peak (post-infusion) serum ALX148 concentrations;","definition_or_measurement_approach":"PK measures of ALX148 including trough (pre-infusion) and peak (post-infusion) serum concentrations."}
• {"endpoint_text":"- Phase II: Immunogenicity characterized by the presence or absence of serum anti-ALX148 antibodies.","definition_or_measurement_approach":"Immunogenicity assessed by detection of anti-ALX148 antibodies in serum."}
• {"endpoint_text":"- Phase III: Objective response rate (ORR), Disease control rate (DCR), duration of response (DoR), and time to tumor progression (TTP) based on both blinded independent central review and investigator assessment.","definition_or_measurement_approach":"Tumor response endpoints assessed by both BICR and investigator per RECIST v1.1."}
• {"endpoint_text":"- Phase III: Progression-free survival (PFS) based on both blinded independent central review and investigator assessment.","definition_or_measurement_approach":"PFS assessed by both BICR and investigator per RECIST v1.1."}
• {"endpoint_text":"- Phase III: Adverse Events as characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v. 5.0), timing, seriousness, and relationship to study therapy.","definition_or_measurement_approach":"Safety assessed by AEs graded per NCI CTCAE v5.0 with timing, seriousness and relationship to therapy."}
• {"endpoint_text":"- Phase III: Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v. 5.0) and timing.","definition_or_measurement_approach":"Laboratory abnormalities summarized by type, frequency, severity per NCI CTCAE v5.0 and timing."}
• {"endpoint_text":"- Phase III: Pharmacokinetic exposure of ALX148 such as trough (pre-infusion) and peak (post-infusion) serum ALX148 concentrations.","definition_or_measurement_approach":"PK measures of ALX148 including trough and peak serum concentrations."}
• {"endpoint_text":"- Phase III: Immunogenicity characterized by the presence or absence of serum anti-ALX148 antibodies.","definition_or_measurement_approach":"Immunogenicity assessed by presence/absence of anti-ALX148 antibodies in serum."}
• {"endpoint_text":"- Phase III: Quality of life measurements as characterized by the EORTC QLQ-C30 and QLQ-STO22 questionnaires.","definition_or_measurement_approach":"Patient-reported quality of life measured using EORTC QLQ-C30 and QLQ-STO22 instruments."}

Belgium

Latest Decision Or Authorization Date

14-08-2024

Number Of Sites

3

Number Of Participants

15

Czechia

Latest Decision Or Authorization Date

01-03-2024

Number Of Sites

3

Number Of Participants

5

France

Latest Decision Or Authorization Date

07-01-2026

Number Of Sites

9

Number Of Participants

25

Italy

Latest Decision Or Authorization Date

01-03-2024

Number Of Sites

5

Number Of Participants

7

Spain

Latest Decision Or Authorization Date

18-12-2025

Number Of Sites

10

Number Of Participants

35

Primary sponsor

Full Name

ALX Oncology Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Syneos Health Inc.

Responsibilities

code: 4 (responsibility code present in CTIS data)

Name

Icon Clinical Research Limited

Responsibilities

codes: 1,11,12,2,8 (responsibility codes present in CTIS data)

Name

Q Squared Solutions LLC / Q Squared Solutions Limited

Responsibilities

Molecular analysis; Immunophenotyping; code: 15 and code: 4 listed

Name

Bioclinica Inc.

Responsibilities

Medical image analysis, primary/surrogate endpoint test

Third parties

• {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"Molecular analysis","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Belgium","full_name":"International Drug Development Institute","duties_or_roles":"codes: 10,14,3,6,7","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"Molecular analysis","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"codes: 1,11,12,2,8","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"Immunophenotyping; code: 4","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Medical image analysis, primary/surrogate endpoint test","organisation_type":"Laboratory/Research/Testing facility"}