Study of Magrolimab in Patients With Solid Tumors (ELEVATELung&UC)

Gilead Sciences

Status and phase: Active, not recruiting; Phase 2

Conditions: Solid Tumor

Treatments: Drug: Docetaxel; Drug: Magrolimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04827576

GS-US-548-5918

2020-005265-14 (EudraCT Number)

Details and patient eligibility

About

The goals of this clinical study are to learn about the safety, tolerability, dosing and effectiveness of magrolimab in combination with docetaxel in patients with solid tumors.

Full description

This study will consist of a Safety Run-in Cohort 1 (magrolimab + docetaxel combination). After completion of the Safety Run-in Cohort 1, Phase 2 Cohort 1 will occur as follows:

• Phase 2 Cohort 1: a cohort of participants with solid tumors (metastatic non-small cell lung cancer (mNSCLC) (Phase 2 Cohort 1a), metastatic urothelial cancer (mUC) (Phase 2 Cohort 1b), and metastatic small cell lung cancer (mSCLC) (Phase 2 Cohort 1c).

Enrollment: 106 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Individual must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
• Adequate blood counts.
• Adequate renal function.
• Adequate liver function.
• Pretreatment blood cross-match completed.
• Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.
• Measurable disease according to RECIST version 1.1

Cohort-Specific Inclusion Criteria:

• Safety Run-in Cohort 1: Individuals with metastatic advanced solid tumors who have had at least 1 prior line of systemic anticancer therapy (metastatic non-small cell lung cancer (mNSCLC) and metastatic small cell lung cancer (mSCLC)) in a locally advanced/metastatic setting, or 2 prior lines of systemic anticancer therapy (metastatic urothelial cancer (mUC)) in a locally advanced/metastatic setting, and not more than 3 prior lines of systemic anticancer therapy in a locally advanced/metastatic setting.
• Phase 2 Cohort 1a (mNSCLC): Individuals with NSCLC who have had treatment with platinum-based chemotherapy and immune checkpoint inhibitor therapy in a locally advanced/metastatic setting, either in combination or sequentially (unless not eligible for one of these therapies) are eligible. At least 1 prior line of systemic anticancer therapy in a locally advanced/metastatic setting is required and not more than 2 prior lines of systemic anticancer therapy in a locally advanced/metastatic setting are allowed. Individuals treated with a taxane within 12 months or individuals refractory to prior taxane treatment are excluded. Individuals whose tumors have genomic alterations are excluded.
• Phase 2 Cohort 1b (mUC): Individuals with UC who have had prior treatment with systemic chemotherapy and immune checkpoint inhibitor therapy in a locally advanced/metastatic setting (unless not eligible for one of these therapies) are eligible. At least 2 prior lines of systemic anticancer therapy in a locally advanced/metastatic setting are required and not more than 3 prior lines of systemic anticancer therapy in a locally advanced/metastatic setting are allowed. Individuals treated with a taxane within 12 months or individuals refractory to prior taxane treatment are excluded.
• Phase 2 Cohort 1c (mSCLC): Individuals with SCLC who have had prior treatment with platinum-based chemotherapy and/or immune checkpoint inhibitor therapy are eligible. At least 1 prior line of systemic anticancer therapy in a locally advanced/metastatic setting is required and not more than 2 prior lines of systemic anticancer therapy in a locally advanced/metastatic setting are allowed. Individuals treated with a taxane within 12 months or individuals refractory to prior taxane treatment are excluded.

Note: Maintenance therapies are not counted as separate lines of therapy.

Key Exclusion Criteria:

• Positive serum pregnancy test.

• Breastfeeding female.

• Active central nervous system (CNS) disease. Individuals with asymptomatic and stable, treated CNS lesions (radiation and/or surgery and/or other CNS-directed therapy who have not received corticosteroids for at least 4 weeks) are allowed.

• Red blood cell (RBC) transfusion dependence, defined as requiring more than 2 units of packed red blood cell transfusions during the 4-week period prior to screening. RBC transfusions are permitted during the screening period and prior to enrollment to meet the hemoglobin inclusion criteria.

• History of hemolytic anemia, autoimmune thrombocytopenia, or Evans syndrome in the last 3 months.

• Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient.

• Prior treatment with cluster of differentiation (CD)47 or signal regulatory protein alpha-targeting agents.

• Current participation in another interventional clinical study.

• Known inherited or acquired bleeding disorders.

• Significant disease or medical conditions, as assessed by the investigator and sponsor, that would substantially increase the risk-benefit ratio of participating in the study. This includes, but is not limited to, acute myocardial infarction within the last 6 months, unstable angina, uncontrolled diabetes mellitus, significant active infections, and congestive heart failure New York Heart Association Class III-IV.

• Second malignancy, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which individuals are not on active anticancer therapies and who are in complete remission for over 3 years.

• Known active or chronic hepatitis B or C infection or human immunodeficiency virus.

• Prior anticancer therapy including but not limited to chemotherapy, immunotherapy, or investigational agents within 4 weeks prior to magrolimab is not permitted.

  • Note: Localized non-CNS radiotherapy, previous hormonal therapy with luteinizing hormone releasing hormone agonists for prostate or breast cancer, and treatment with bisphosphonates and receptor activator of nuclear factor kappa B ligand (RANKL) inhibitors are not criteria for exclusion.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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106 participants in 4 patient groups

Safety Run-in Cohort 1, mNSCLC, mUC, mSCLC (Magrolimab + Docetaxel)

Experimental group

Description:

Participants with solid tumors (metastatic non-small cell lung cancer (mNSCLC), metastatic urothelial cancer (mUC), metastatic small cell lung cancer (mSCLC)) will receive an escalating dose of magrolimab and docetaxel.

Treatment:

Drug: Magrolimab

Drug: Docetaxel

Phase 2 Cohort 1a, mNSCLC (Magrolimab + Docetaxel)

Experimental group

Description:

Participants with mNSCLC will receive magrolimab at the recommended Phase 2 dose (RP2D) determined in the Safety Run-in Cohort 1 and docetaxel.

Treatment:

Drug: Magrolimab

Drug: Docetaxel

Phase 2 Cohort 1b, mUC (Magrolimab + Docetaxel)

Experimental group

Description:

Participants with mUC will receive magrolimab at the RP2D determined in the Safety Run-in Cohort 1 and docetaxel.

Treatment:

Drug: Magrolimab

Drug: Docetaxel

Phase 2 Cohort 1c, mSCLC (Magrolimab + Docetaxel)

Experimental group

Description:

Participants with mSCLC will receive magrolimab at the RP2D determined in the Safety Run-in Cohort 1 and docetaxel.

Treatment:

Drug: Magrolimab

Drug: Docetaxel