Evaluate the Safety, Tolerability, and Preliminary Efficacy of EVM14 Alone and in Combination in Patients With Selected Solid Tumors

Everest Medicines (Beijing) Co., Ltd.

Status and phase: Not yet enrolling; Phase 2; Phase 1

Conditions: Selected Types of Solid Tumor

Treatments: Biological: EVM14; Combination Product: Pembrolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT07095868

EVM14C101

Details and patient eligibility

About

Brief Summary:

The purpose of this clinical trial is to evaluate the safety, tolerability, preliminary efficacy, and immunogenicity of EVM14 administered intramuscularly (IM) alone and in combination with pembrolizumab in patients with selected solid tumors.

Full description

EVM14C101 study is a First in Human(FIH), open-label, multiregional, multicenter study conducted in 2 Phases: Phase I and Phase IIa. In Phase I, EVM14 will be administered intramuscularly(IM) as a monotherapy (Mono Cohort) and in combination with pembrolizumab (Combo Cohort) in patients with solid tumors to assess the safety and tolerability, immunogenicity, preliminary efficacy of EVM14 as monotherapy and in combination with pembrolizumab. Based on the safety and immunogenicity data of Phase I, dose of EVM14 will be selected for the Phase IIa. In Phase IIa, the safety and tolerability, preliminary efficacy, and immunogenicity of EVM14 in combination with pembrolizumab will be further assessed in patients with solid tumors.

Enrollment: 94 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Selected types of solid tumor that are pathologically confirmed unresectable advanced, recurrent, or metastatic.
2. Patients with at least 1 evaluable lesion assessed by Investigators within 28 days prior to the first dose of study treatment as defined per RECIST v1.1.
3. Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1 at Screening.
4. Life expectancy ≥ 3 months.
5. Patients must have adequate organ function.
6. At screening, patients must agree to provide, if available, tumor tissue for biomarker analysis. When archival tumor tissue is not available, it is optional for the patient to undergo a fresh biopsy to collect tumor tissue if deemed medically safe by the Investigator.

Exclusion criteria

1. Has disease that is suitable for local treatment administered with curative intent.
2. Has a diagnosed and/or treated additional malignancy within 5 years prior to the first dose of study treatment except for: curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, and curatively resected in situ breast, cervical cancer, and prostate cancer.
3. Histologically/cytologically confirmed nasopharynx cancer. Has non-squamous histology NSCLC. If small cell elements are present, the patient is ineligible.
4. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
5. Has a diagnosis of immunodeficiency.
6. Use of systemic corticosteroid (> 10 mg/day prednisone or equivalent) or other immunosuppressive medication within 14 days before the first dose of study treatment.
7. Has active autoimmune disease that has required systemic treatment in past 2 years or history of autoimmune disease that has possibility of relapse or at risk of having these conditions.
8. Poorly controlled co-morbidity, including but not limited to poorly controlled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg) and poorly controlled type 2 diabetes, or other serious conditions requiring systemic treatment. Active gastric or duodenal ulcer.
9. Cerebrovascular events (stroke, transient ischemic attack, etc.) within 6 months prior to the first dose of study treatment.
10. QTcF interval male > 450 msec; female > 470 msec Or serious cardiovascular disease within 6 months prior to the first dose of study treatment
11. The left ventricular ejection fraction (LVEF) < 50% during the screening period.
12. History of Stevens-Johnson syndrome or toxic epidermal necrolysis syndrome.
13. Patients known to be human immunodeficiency virus (HIV)-positive or have acquired immune deficiency syndrome (AIDS).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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94 participants in 7 patient groups

Phase I Dose Escalation in Monotherapy Cohort

Experimental group

Description:

EVM14 will be administered at every 2 weeks (Q2W) if disease progression doesn't occur.

Treatment:

Biological: EVM14

Phase I Dose Escalation in Combination Therapy Cohort

Experimental group

Description:

EVM14 will be administered intramuscularly (IM) every 3 weeks (Q3W) + pembrolizumab 200 mg administered intravenously (IV infusion) Q3W if disease progression doesn't occur.

Treatment:

Combination Product: Pembrolizumab

Biological: EVM14

Phase IIa Dose Level A for tumor type 1

Experimental group

Description:

For patients with tumor type 1, EVM14 in Dose Level A will be administered intramuscularly (IM) every 3 weeks (Q3W) + pembrolizumab 200 mg administered intravenously (IV infusion) Q3W if disease progression doesn't occur.

Treatment:

Combination Product: Pembrolizumab

Biological: EVM14

Phase IIa Dose Level B for tumor type 1

Experimental group

Description:

For patients with tumor type 1, EVM14 in Dose Level B will be administered intramuscularly (IM) every 3 weeks (Q3W) + pembrolizumab 200 mg administered intravenously (IV infusion) Q3W if disease progression doesn't occur.

Treatment:

Combination Product: Pembrolizumab

Biological: EVM14

Phase IIa Control for tumor type 1

Active Comparator group

Description:

For patients with tumor type 1, pembrolizumab 200 mg alone will be administered intravenously (IV infusion) every 3 weeks (Q3W) if disease progression doesn't occur.

Treatment:

Biological: EVM14

Phase IIa Experimental for tumor type 2

Experimental group

Description:

For patients with tumor type 2, EVM14 in a selected Dose Level will be administered intramuscularly (IM) every 3 weeks (Q3W) + pembrolizumab 200 mg administered intravenously (IV infusion) Q3W if disease progression doesn't occur.

Treatment:

Combination Product: Pembrolizumab

Biological: EVM14

Phase IIa Control for tumor type 2

Active Comparator group

Description:

For patients with tumor type 2, pembrolizumab 200 mg alone will be administered intravenously (IV infusion) every 3 weeks (Q3W) if disease progression doesn't occur.

Treatment:

Biological: EVM14