A Study of Evorpacept (ALX148) in Patients With Advanced HER2+ Gastric Cancer (ASPEN-06)

Study Overview
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Brief Summary
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A Phase 2/3 Study of Evorpacept (ALX148) in Combination With Trastuzumab, Ramucirumab, and Paclitaxel in Patients With Advanced HER2-overexpressing gastric/GEJ adenocarcinoma.

Detailed Description
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This is a randomized phase 2 (open-label) / 3 (double-blind), international, multi-center study of patients with metastatic HER2-overexpressing gastric/GEJ adenocarcinoma that has progressed on or after prior HER2-directed therapy and fluoropyrimidine- or platinum-containing chemotherapy and are suitable for chemotherapy (2nd-line or 3rd-line). Approximately 450 adult patients are expected to be enrolled in the study across both phases.

Official Title
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A Phase 2/3 Study of Evorpacept (ALX148) in Patients With Advanced HER2-Overexpressing Gastric/Gastroesophageal Junction Adenocarcinoma (ASPEN-06)

Conditions
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Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, Gastric Adenocarcinoma

Intervention / Treatment
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* Drug: Evorpacept (ALX148)
* Drug: Trastuzumab
* Drug: Ramucirumab
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) Adequate Bone Marrow Function. Adequate Renal & Liver Function. Adequate Performance Status Exclusion Criteria: Patients with known symptomatic CNS metastases or leptomeningeal disease requiring steroids. Prior treatment with any anti-CD47 or anti-SIRPα agent. Prior treatment with ramucirumab.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 2 - Arm A<br>Evorpacept (ALX148) 30 mg/kg Q2W IV, trastuzumab (initial dose of 6 mg/kg followed by 4 mg/kg) Q2W IV, ramucirumab 8 mg/kg Q2W IV, and paclitaxel 80 mg/m2 IV Days 1, 8, and 15 of a 28-day cycle. | Drug: Evorpacept (ALX148)<br>* IV Q2W<br>Drug: Trastuzumab<br>* IV Q2W<br>* Other names: Herceptin;Drug: Ramucirumab<br>* IV Q2W<br>* Other names: Cyramza;Drug: Paclitaxel<br>* IV Days 1, 8, and 15 of a 28-day cycle<br>* Other names: Taxol;|
| Active Comparator: Phase 2 - Arm B<br>Trastuzumab (initial dose of 6 mg/kg followed by 4 mg/kg) Q2W IV, ramucirumab 8 mg/kg Q2W IV, and paclitaxel 80 mg/m2 IV Days 1, 8, and 15 of a 28-day cycle. | Drug: Trastuzumab<br>* IV Q2W<br>* Other names: Herceptin;Drug: Ramucirumab<br>* IV Q2W<br>* Other names: Cyramza;Drug: Paclitaxel<br>* IV Days 1, 8, and 15 of a 28-day cycle<br>* Other names: Taxol;|
| Experimental: Phase 3 - Arm A<br>Evorpacept (ALX148) 30 mg/kg Q2W IV, trastuzumab (initial dose of 6 mg/kg followed by 4 mg/kg) Q2W IV, ramucirumab 8 mg/kg Q2W IV, and paclitaxel 80 mg/m2 IV Days 1, 8, and 15 of a 28-day cycle. | Drug: Evorpacept (ALX148)<br>* IV Q2W<br>Drug: Trastuzumab<br>* IV Q2W<br>* Other names: Herceptin;Drug: Ramucirumab<br>* IV Q2W<br>* Other names: Cyramza;Drug: Paclitaxel<br>* IV Days 1, 8, and 15 of a 28-day cycle<br>* Other names: Taxol;|
| Active Comparator: Phase 3 - Arm B<br>Ramucirumab 8 mg/kg Q2W IV and paclitaxel 80 mg/m2 IV Days 1, 8, and 15 of a 28-day cycle. | Drug: Ramucirumab<br>* IV Q2W<br>* Other names: Cyramza;Drug: Paclitaxel<br>* IV Days 1, 8, and 15 of a 28-day cycle<br>* Other names: Taxol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 2 | Percentage of patients with objective response per RECIST 1.1 | Last randomized patient on study at least 16 weeks | 
| Phase 3 | Overall Survival | From the date of randomization to the date of death (due to any cause), up to 36 months postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ramucirumab, Evorpacept, ALX148, CD47, SIRPα, Gastric, Gastroesophageal, GEJ, HER2 positive