A Study of Evorpacept (ALX148) in Patients with Advanced Gastric Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alx Oncology Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

24 Jan 2022 → ongoing

Decision date (initial)

2024-02-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

ALX Oncology Inc.

External identifiers

EU CT number

2023-509406-30-00

EudraCT number

2021-001008-14

ClinicalTrials.gov

NCT05002127

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Pharmacogenomic, Pharmacodynamic, Pharmacokinetic, Efficacy

Phase II:
1. To assess the effect of ALX148 plus trastuzumab, ramucirumab, and paclitaxel on objective response rate (ORR), compared to a historical control with a combination of ramucirumab and paclitaxel, in patients with metastatic HER2-overexpressing gastric/GEJ adenocarcinoma that has progressed on or after a prior HER2-directed agent and fluoropyrimidine- or platinum-containing chemotherapy.
2. To assess the contribution of ALX148 to a regimen of trastuzumab, ramucirumab, and paclitaxel, as measured by the difference in ORR between the two randomized treatment arms, in patients with metastatic HER2-overxpressing gastric/GEJ adenocarcinoma that has progressed on or after a prior HER2-directed agent and fluoropyrimidine- or platinum-containing chemotherapy.

Phase III:
1. To assess the effect of ALX148 plus trastuzumab, ramucirumab, and paclitaxel versus ramucirumab and paclitaxel on overall survival (OS) in patients with metastatic HER2-overexpressing gastric/GEJ adenocarcinoma that has progressed on or after a prior HER2-directed agent and fluoropyrimidine- or platinum-containing chemotherapy.

Secondary objectives 5

1. Phase II: To assess the effect of ALX148 plus trastuzumab, ramucirumab, and paclitaxel on objective response rate (ORR) using blinded independent central review (BICR).
2. Phase II: To assess secondary measures of efficacy for ALX148 administered in combination with trastuzumab, ramucirumab, and paclitaxel versus trastuzumab, ramucirumab, and paclitaxel.
3. Phase II: To assess the safety and tolerability of ALX148 administered in combination with trastuzumab, ramucirumab, and paclitaxel versus trastuzumab, ramucirumab, and paclitaxel.
4. Phase II: To characterize the pharmacokinetics (PK) and evaluate the immunogenicity of ALX148.
5. Phase III (in addition to above): To assess the impact of ALX148 administered in combination with trastuzumab, ramucirumab, and paclitaxel versus ramucirumab and paclitaxel on patient reported outcomes of quality of life

Conditions and MedDRA coding

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)

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Age ≥18 years (except in regions in which the minimum age for subject participation is >18 years)
2. 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)
3. 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
4. Adequate bone marrow, renal, liver, cardiac (via ECG), clotting (INR/PT and PTT) function
5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) must be 0 or 1
6. Resolved acute effects of any prior therapy
7. Patients of childbearing potential must be non-pregnant and must agree to use a highly effective method of contraception throughout the study
8. Consent to the study and study procedures

Exclusion criteria 6

1. 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
2. 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
3. Prior treatment with anti-CD47 or anti-SIRPα agent or ramucirumab or any other systemic anticancer therapy within 4 weeks of starting study treatment
4. 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
5. 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
6. Prior history of GI perforation/fistula (within 6 months of first dose of protocol therapy) or risk factors for perforation

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 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.
2. Phase III: Overall survival (OS)

Secondary endpoints 14

1. 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).
2. Phase II: Duration of response (DoR), disease control rate (DCR), time to tumor progression (TTP) based on investigator and BICR assessment.
3. Phase II: Progression-free survival (PFS) based on investigator and BICR assessment, and overall survival (OS).
4. 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;
5. Phase II: Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v. 5.0) and timing.
6. Phase II: Pharmacokinetic exposure of ALX148 such as trough (pre-infusion) and peak (post-infusion) serum ALX148 concentrations;
7. Phase II: Immunogenicity characterized by the presence or absence of serum anti-ALX148 antibodies.
8. 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.
9. Phase III: Progression-free survival (PFS) based on both blinded independent central review and investigator assessment.
10. 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.
11. Phase III: Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v. 5.0) and timing.
12. Phase III: Pharmacokinetic exposure of ALX148 such as trough (pre-infusion) and peak (post-infusion) serum ALX148 concentrations.
13. Phase III: Immunogenicity characterized by the presence or absence of serum anti-ALX148 antibodies.
14. Phase III: Quality of life measurements as characterized by the EORTC QLQ-C30 and QLQ-STO22 questionnaires.

Investigational products

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

Test 1

Comparator 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alx Oncology Inc.

Sponsor organisation

Alx Oncology Inc.

Address

323 Allerton Avenue

City

South San Francisco

Postcode

94080-4816

Country

United States

Scientific contact point

Organisation

Alx Oncology Inc.

Contact name

ALX Oncology Inc.

Public contact point

Organisation

Alx Oncology Inc.

Contact name

ALX Oncology Inc.

Third parties 7

Locations

5 EU/EEA countries · 30 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

Documents 53 files

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

Application history

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