FGFR4 Inhibitor EVER4010001 in Combination With PD-1 Inhibitor Pembrolizumab in Patients With Advanced Solid Tumors

NCT04699643 | Unknown Phase 1 DMC

• 1 other identifier: EVER401-001
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of EVER4010001 in combination with Pembrolizumab in Patients with Advanced Solid Tumors. And in phase II to assess the anti-tumor efficacy of EVER4010001 in combination with Pembrolizumab in treating selected indications using appropriate biomarkers.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicities (DLTs) observed in combined administration of EVER4010001 and Pembrolizumab

  Dose-limiting toxicities (DLTs) observed in combined administration of EVER4010001 and Pembrolizumab

  up to 12 months

• Objective response rate (ORR) by IRC according to RECIST v 1.1

  Objective response rate (ORR) by IRC according to RECIST v 1.1

  3 years

Secondary Outcomes (11)

• PK parameters of EVER4010001: maximum observed concentration (Cmax)

  3 years

• Objective response rate (ORR)

  3 years

• Disease control rate (DCR)

  3 years

• Duration of response (DOR)

  3 years

• Adverse events (AEs) and serious adverse events (SAEs) defined by National Cancer Institute-Common terminology criteria for adverse events (NCI-CTCAE) v5.0

  3 years

Study Arms (1)

EVER4010001 combination with Pembrolizumab

EXPERIMENTAL

EVER4010001 combination with Pembrolizumab, EVER4010001 started dose escalation from 40mg bid, and then to 60mg bid, 80mg bid, 100mg bid and 120 mg bid if applicable, dose escalation decision will be made by safety monitoring committee which is composed of the study team members. After phase II dose was recommended by safety monitoring committee, this dose will be applied to phase II patients. Pembrolizumab will be administered at 200mg every 3 weeks through the study.

Drug: EVER4010001

Interventions

EVER4010001 DRUG

Please refer to information in arm/group descriptions.

Also known as: Pembrolizumab

EVER4010001 combination with Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be obtained prior to any procedures that are related to this study.
• Patients (male or female) ≥ 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status≤1
• Presence of at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Phase I study part: Histologically or cytologically confirmed metastatic or locally advanced solid tumors, for which no standard therapy exits or the standard therapy has failed.
• Phase II study part: 1. Histologically or cytologically confirmed metastatic or locally advanced solid tumors of the selected indications. 2. Positive FGF19 in IHC test results of tumor tissues in pre-screening.

You may not qualify if:

• Prior therapies within the following time frames prior to the first dose of study treatment:
• Last dose of conventional cytotoxic chemotherapy: ≤4 weeks ((≤ 6 weeks for nitrosoureas and mitomycin-C);
• Drugs with anti-tumor activity (e.g., antibodies): ≤4 weeks
• Non-cytotoxic small molecule therapeutics (e.g., sorafenib): ≤5 half-lives or ≤2 weeks (whichever is longer)
• Previous wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) ≤ 4 weeks and limited field radiation for palliation ≤ 2 weeks (including particle implantation such as I125);
• Participation in a prior investigational study: ≤ 4 weeks;
• Drugs with immunomodulatory activity (such as thymosin, interferon, interleukin, etc.) ≤ 6 weeks.
• Major surgery within 4 weeks of receiving the first dose of study treatment (mediastinoscopy, insertion of a central venous access device and insertion of a feeding tube are not considered major surgery).
• Subject having out of range laboratory values including hematology, chemistry and coagulation indicators. See Section 5.3 for specific indicators.
• Use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GM-CSF, M CSF), blood transfusion products (e.g., whole blood, plasma, apheresis platelets, etc.), thrombopoietin mimetics or erythroid stimulating agents ≤ 2 weeks prior to start of study treatment. If erythroid stimulating agents were initiated more than 2 weeks prior to the first dose of study treatment and the patient is on a stable dose, they can be maintained.
• Symptomatic CNS metastases which are neurologically unstable, or CNS metastases requiring local CNS directed therapy (such as radiotherapy or surgery), or increasing doses of corticosteroids within 2 weeks of first dose of study treatment.
• Serous effusion with clinically significant symptoms (such as shortness of breath, abdominal distention, etc.).
• Major acute or chronic infections, including:
• Positive human immunodeficiency virus (HIV) antibody screening or known acquired immunodeficiency syndrome (AIDS);
• Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection: positive HBV-DNA copies (\>2000 IU/mL) and/or other activity indicators; positive HCV antibody and HCV-RNA test result;

Sponsors & Collaborators

• EverNov Medicines (Zhuhai Hengqin) Co., Ltd: lead
• Medidata Solutions: collaborator

Study Sites (1)

Department of Gastrointestinal Oncology, the Fifth Medical Center, Chinese PLA General Hospital

Beijing, Beijing Municipality, 100071, China

RECRUITING

MeSH Terms

Interventions

pembrolizumab

Study Officials

• Jianming Xu

  Department of Gastrointestinal Oncology, the Fifth Medical Center, Chinese PLA General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mingxia Liu

CONTACT

+86 10 65350128; mingxia.liu@everestmedicines.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2020
• First Posted: January 7, 2021
• Study Start: July 30, 2020
• Primary Completion: June 1, 2023
• Study Completion: June 1, 2023
• Last Updated: January 7, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)