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

Official title

A Phase I/IIa Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of EVM14 as Monotherapy and in Combination With Pembrolizumab in Patients With Selected Solid Tumors

Overview

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.

Detailed 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.

Interventions

• Biological EVM14
  Cancer Vaccine
• Combination product Pembrolizumab
  Anti-PD1 antibody

Primary outcome measures

• Phase I and Phase IIa: Incidence and severity of adverse events [Time frame: From the the start of the first dose of study treatment to 90 days after the last study treatment or new anti-cancer treatments started, whichever occurs earlier.]
• Phase I: Incidence of dose-limiting toxicities (DLT) [Time frame: Mono cohort: 28-day period from the first EVM14 monotherapy dose. Combo cohort: Days 1 to 21: 21-day period from the first dose of EVM14 in combination with pembrolizumab.]
• Phase IIa tumor type 1: Progression-free survival (PFS) [Time frame: From the baseline to disease progression confirmed by radiological examination, the start of a new anti-cancer treatment, withdrawal of informed consent, lost to follow-up, death, or end of study, whichever occurs first. (Up to 3 years)]

Secondary outcome measures (5)

• Phase I and Phase IIa: Objective response rate (ORR) [Time frame: From the baseline to disease progression confirmed by radiological examination, the start of a new anti-cancer treatment, withdrawal of informed consent, lost to follow-up, death, or end of study, whichever occurs first. (Up to 3 years.)]
• Phase I and Phase IIa: Disease control rate (DCR) [Time frame: From the baseline to disease progression confirmed by radiological examination, the start of a new anti-cancer treatment, withdrawal of informed consent, lost to follow-up, death, or end of study, whichever occurs first. (Up to 3 years.)]
• Phase I and Phase IIa: Duration of response (DOR) [Time frame: From the baseline to disease progression confirmed by radiological examination, the start of a new anti-cancer treatment, withdrawal of informed consent, lost to follow-up, death, or end of study, whichever occurs first. (Up to 3 years.)]
• Phase I and Phase IIa tumor type 2: Progression Free Survival (PFS) [Time frame: From the baseline to disease progression confirmed by radiological examination, the start of a new anti-cancer treatment, withdrawal of informed consent, lost to follow-up, death, or end of study, whichever occurs first. (Up to 3 years.)]
• Phase IIa: Time to response (TTR) [Time frame: From the baseline to disease progression confirmed by radiological examination, the start of a new anti-cancer treatment, withdrawal of informed consent, lost to follow-up, death, or end of study, whichever occurs first. (Up to 3 years.)]

Eligibility criteria

Inclusion criteria

• Selected types of solid tumor that are pathologically confirmed unresectable advanced, recurrent, or metastatic.
• 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.
• Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1 at Screening.
• Life expectancy ≥ 3 months.
• Patients must have adequate organ function.
• 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

• Has disease that is suitable for local treatment administered with curative intent.
• 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.
• Histologically/cytologically confirmed nasopharynx cancer. Has non-squamous histology NSCLC. If small cell elements are present, the patient is ineligible.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has a diagnosis of immunodeficiency.
• Use of systemic corticosteroid (> 10 mg/day prednisone or equivalent) or other immunosuppressive medication within 14 days before the first dose of study treatment.
• 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.
• 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.
• Cerebrovascular events (stroke, transient ischemic attack, etc.) within 6 months prior to the first dose of study treatment.
• QTcF interval male > 450 msec; female > 470 msec Or serious cardiovascular disease within 6 months prior to the first dose of study treatment
• The left ventricular ejection fraction (LVEF) < 50% during the screening period.
• History of Stevens-Johnson syndrome or toxic epidermal necrolysis syndrome.
• Patients known to be human immunodeficiency virus (HIV)-positive or have acquired immune deficiency syndrome (AIDS).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 4 centers

• Hunan Cancer Hospital — Changsha
• Nanjing Drum Tower Hospital — Nanjing
• The First Affiliated Hospital With Nanjing Medical University — Nanjing
• Shanghai Pulmonary Hospital — Shanghai

United States · 3 centers

• Memorial Sloan Kettering Cancer Center — New York
• MD Anderson Cancer Center — Houston
• NEXT Oncology — Fairfax

Identifiers

NCT: NCT07095868 · EVM14C101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗