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Advanced Solid TumorsPhase 1/2NCT04699643

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

A Phase 1/2 study testing EVER4010001 in people with Advanced Solid Tumors, run by EverNov Medicines (Zhuhai Hengqin) Co., Ltd at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Solid Tumors
What is being tested?
EVER4010001
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
1 siteChina
Study dates
30 Jul 2020to Jun 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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;
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  • 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.
  • Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 5 years prior to study entry; completely resected basal cell and squamous cell skin cancers and completely resected carcinoma in situ of any type.
  • 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;
  • active TB (such as exposure history or positive TB test; AND clinical symptoms, physical or imaging manifestations);
  • Ongoing antibiotic treatment of serious acute infections.
  • Previous treatment with a selective FGF19-FGFR4 targeted therapy and/or pan-FGFR inhibitor.
  • Patients receiving treatment with cytochrome P450 (CYP)1A2, CYP2C9 and CYP3A4/5 substrates with a narrow therapeutic index (NTI) that cannot be discontinued for the duration of the study.
  • Patients receiving known BSEP efflux transporter inhibitors that cannot be discontinued 3 days prior to the start of study treatment and during the course of the study.
  • Current evidence of calcium-phosphate homeostasis impairment. See Section 5.3 for specific indicators.
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral EVER4010001 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, small bowel resection).
  • Ongoing active diarrhea requiring medications (e.g. bile acid sequestrant (BAS), loperamide).
  • Irritable bowel syndrome with signs/symptoms or requires medications.
  • Any previous specific target T cell co-stimulation or immune checkpoint pathway treatment, including but not limited to PD-1 inhibitors, PD-L1 / 2 inhibitors or other targeted T cell drugs.
  • Use of systemic chronic steroid therapy (≥ 10mg/day prednisone or equivalent) or any immunosuppressive therapy two weeks prior to start of study treatment. Topical, inhaled, nasal and ophthalmic steroids are allowed.
  • Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment (except inactivated seasonal influenza vaccines).
  • Active known or suspected autoimmune disease. Patients with vitiligo, residual hypothyroidism only requiring hormone replacement, or psoriasis not requiring systemic treatment can be included.
  • History of severe hypersensitivity reactions to any ingredient of study treatment and other monoclonal antibodies (mAbs) and/or their excipients.
  • Impaired cardiac function or clinically significant cardiac disease, including any of the following:
  • -Clinically significant or uncontrolled heart disease such as congestive heart failure requiring treatment (New York Heart Association Grade ≥ 2), uncontrolled hypertension (defined by Systolic Blood Pressure > 160 mmHg/ Diastolic Blood Pressure > 100mmHg (average of three consecutive readings) at rest despite medical treatment, clinically significant arrhythmia; QTcF > 470 msec on screening ECG or congenital long QT syndrome; acute myocardial infarction or unstable angina pectoris < 3 months prior to screening.
  • History of liver or other organ transplantation.
  • History of interstitial lung disease or pneumonia requiring oral or intravenous steroids.
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.
  • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing with study treatment and for the following duration after discontinuation of study treatment: See Section 5.3 for specific contraception methods.
  • Sexually active males unless they use a condom during intercourse while receiving study treatment and for the following period after the last dose of study treatment, and should not father a child in this period.
  • Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures. Any severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study treatment administration or that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for the study.

Trial locations and contacts

1 site in 1 country.

Mingxia Liu contact

+86 10 65350128

mingxia.liu@everestmedicines.com

China1 site, 1 recruiting

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

    Beijing, Beijing Municipality, 100071

    Jianming Xu, Doctor, +86-10-66947120, Jmxu2003@163.com

    Recruiting

Other trials in China

About this study

Official title: A Phase I/II Study of FGFR4 Inhibitor EVER4010001 in Combination With PD-1 Inhibitor Pembrolizumab in Patients With Advanced Solid Tumors With Dose Escalation and Expansion to Selected Indications

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.

Read the detailed description

This is a phase I/II, single arm, multicenter study of EVER4010001 combination with Pembrolizumab in advanced solid tumor patients. The primary endpoint of phase I will be Dose-limiting toxicities (DLTs) observed in combined administration of EVER4010001 and Pembrolizumab. And the primary endpoint of phase II will be the ORR per RECIST v1.1 in all treated patients.

Patients will be treated until progression requiring discontinuation of further treatment, unacceptable toxicity, study withdrawal, or death, whichever comes first. Tumor response and progression will be assessed using RECIST v1.1 and assessment by investigator at the trail center will be sufficient for decisions on continuation of treatment. All patients will visit the investigator at regular intervals for assessment of safety parameters and AEs.

Being tested
EVER4010001

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EVER4010001Drug

    Also called Pembrolizumab

    Please refer to information in arm/group descriptions.

Study groups in NCT04699643
Study groupRoleWhat they receive
EVER4010001 combination with PembrolizumabExperimentalEVER4010001 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.
Receives: Drug: EVER4010001

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

    Measured: up to 12 months

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

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

    Measured: 3 years

Secondary outcomes (11)

  1. PK parameters of EVER4010001: maximum observed concentration (Cmax)

    PK parameters of EVER4010001: maximum observed concentration (Cmax)

    Measured: 3 years

  2. Objective response rate (ORR)

    Objective response rate (ORR)

    Measured: 3 years

  3. Disease control rate (DCR)

    Disease control rate (DCR)

    Measured: 3 years

  4. Duration of response (DOR)

    Duration of response (DOR)

    Measured: 3 years

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

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

    Measured: 3 years

  6. Exploratory biomarkers include Total bile acids, 7-α-hydroxy-4-cholesten-3-one (C4), circulating FGF19, etc.

    Exploratory biomarkers include Total bile acids, 7-α-hydroxy-4-cholesten-3-one (C4), circulating FGF19, etc.

    Measured: 3 years

  7. Progression-free survival (PFS)

    Progression-free survival (PFS)

    Measured: 3 years

  8. Overall survival (OS)

    Overall survival (OS)

    Measured: 3 years

  9. Immunogenicity of Pembrolizumab: anti-drug antibody (ADA)

    Immunogenicity of Pembrolizumab: anti-drug antibody (ADA)

    Measured: 3 years

  10. FGF19 expression in tumor cells and tumor microenvironment cells by immunohistochemical testing

    FGF19 expression in tumor cells and tumor microenvironment cells by immunohistochemical testing

    Measured: 3 years

  11. PK parameters of EVER4010001: area under the concentration-time curve (AUC)

    PK parameters of EVER4010001: area under the concentration-time curve (AUC)

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jan 2021
  2. Study start30 Jul 2020
  3. Primary completionJun 2023 (estimated)
  4. Study completionJun 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
80 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04699643
Sponsor's protocol ID
EVER401-001
Status last verified
Jan 2021
First submitted
29 Dec 2020
Last updated
7 Jan 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing EVER4010001 in people with Advanced Solid Tumors, run by EverNov Medicines (Zhuhai Hengqin) Co., Ltd at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 7 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Mingxia Liu (+86 10 65350128, mingxia.liu@everestmedicines.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting toxicities (DLTs) observed in combined administration of EVER4010001 and Pembrolizumab (time frame: up to 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04699643.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2021.

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