A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Evidence of Antitumor Activity of FHND5071 as a Single Agent in Adult Patients With Advanced Solid Tumors

NCT05818917 | Unknown Phase 1

• 1 other identifier: FHND5071-I-01
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase 1, first-in-human, open-label dose-escalation study to determine the MTD and/or recommended Phase 2 dose (RP2D) and assess the DLT of FHND5071. The safety, tolerability, and PK of FHND5071 will be assessed in adult patients with advanced solid tumors. The total number of evaluable subjects in the study will depend upon the number of dose-escalations necessary. It is estimated that approximately 24 evaluable subjects will be enrolled in the dose-escalation part of this study. This multicenter study will be conducted in the United States. Dose-escalation of FHND5071 will follow two sequential parts:

1. 1.a modified accelerated titration design in single subject cohorts with a starting dose level of 40 mg, where the FHND5071 dose would be doubled in each dose cohort until the subject in a current cohort experience a Grade ≥2 adverse event that is at least possibly related to FHND5071 in the opinion of the Investigator and the Medical Monitor;
2. 2.a modified 3+3 escalation design in cohort of 3-6 subjects, where the FHND5071 dose would be escalated in ≤100% increments determined by the Safety Review Committee (SRC) until 2 of 3 or 2 of 6 subjects experience a DLT. In both parts of dose escalation, FHND5071 will be administered orally once daily (QD) in 28-day treatment cycles.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (1)

• Number of Participants Reporting One or More Treatment-Emergent Adverse Events and Serious Adverse Events

  An Adverse Event is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A Serious Adverse Event (SAE) was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

  Baseline to 28 days after first dose of FHND5071 administration

Study Arms (6)

40mg

EXPERIMENTAL

FHND5071, 40mg, tablet, orally, once daily

Drug: FHND5071

80mg

EXPERIMENTAL

FHND5071,80mg, tablet, orally, once daily

Drug: FHND5071

160mg

EXPERIMENTAL

FHND5071, 160mg, tablet, orally, once daily

Drug: FHND5071

240mg

EXPERIMENTAL

FHND5071, 240mg, tablet, orally, once daily

Drug: FHND5071

320mg

EXPERIMENTAL

FHND5071, 320mg, tablet, orally, once daily

Drug: FHND5071

400mg

EXPERIMENTAL

FHND5071, 400mg, tablet, orally, once daily

Drug: FHND5071

Interventions

FHND5071 DRUG

The proposed starting dose is 40 mg FHND5071 once daily (QD) orally (PO). For the purposes of this study treatment cycles will be 28 days or 4 weeks. FHND5071 will be administered orally in the morning following a fast of approximately 10 hours before dosing on PK collection days. Subjects will continue to fast for approximately 4 hours after the administration of FHND5071. On non-PK days the subjects will fast approximately 2 hours before FHND5071 and continue to fast for approximately 2 hours afterwards. Other dosing regimens may be considered based on the analysis of emerging PK, progressive disease, and/or safety data.

160mg; 240mg; 320mg; 400mg; 40mg; 80mg

Eligibility Criteria

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

You may qualify if:

• The subjects agree and have the ability to comply with the study and follow-up procedures. Before any examination and study, the subjects or their legal guardians shall sign and date a written informed consent;
• Age ≥ 18 years old, male or female;
• The Eastern Cooperative Oncology Group Performance Status (ECOG PS) score is 0\~1;
• The expected survival period is not less than 12 weeks;
• Subjects have at least one evaluable lesion according to RECIST V1.1. Tumor lesions that have progressed after being irradiated ≥4 weeks before the start of treatment can be used as target lesions in the absence of non-irradiated evaluable lesions;
• Subjects with advanced solid tumors confirmed by histology or cytology, for whom the standard treatment has failed, or there is no standard treatment regime, or the standard treatment is not applicable at the current stage;
• Subjects must have adequate organ functions, as defined below:
• Liver function:
• Serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT) ≤ 2.5 times the upper limit of normal (ULN); total serum bilirubin (TBIL) ≤ 1.5 times ULN (for subjects with Gilbert syndrome, serum bilirubin ≤ 3.0 × ULN).
• Bone marrow function (no blood transfusion or hematopoietic stimulating factor therapy within 10 days prior to testing):
• Absolute neutrophil count (ANC) ≥1.5×109/L;
• Platelet (PLT) ≥100×109/L;
• Hemoglobin (Hb) ≥9g/dL;
• Lymphocyte count ≥0.5×109/L.
• Kidney function:

You may not qualify if:

• Subjects who meet any of the following will not be able to enter this study:
• Previous (≤3 years) or current existence of cancer histologically determined to be different from the study tumors, except for cervical carcinoma in situ, superficial non-invasive bladder tumor, or cured stage I non-melanoma skin cancer;
• Subjects carrying known major mutational driver genes other than RET gene, such as: EGFR, ALK, ROS1, etc.;
• Known severe allergy to the study drug or excipient (microcrystalline cellulose);
• Severe autoimmune diseases (including immune-related AEs from previous immuno-oncology therapy) or autoimmune diseases requiring chronic systemic corticosteroid therapy with immunosuppressive doses (prednisone \>10 mg/day or equivalent);
• Known malignant central nervous system diseases, except for neurologically stable and treated brain metastases, which are defined as brain metastases that have been treated with surgery, surgery plus radiotherapy, or radiotherapy alone, with no signs of progression or hemorrhage within 14 days after treatment and all systemic corticosteroids discontinued within 14 days prior to the treatment.
• Medical history (within 6 months before treatment initiation) or evidence of pericarditis (of any grade) or pericardial effusion (≥ Grade 2);
• Medical history (within 6 months prior to initiation of therapy) or evidence of interstitial lung disease, radiation pneumonitis or idiopathic pulmonary fibrosis requiring steroid therapy, pleural or pericardial effusion requiring intervention such as drainage.
• Medical history (within 4 weeks after initiation of therapy) or evidence of active infection (≥ Grade 2);
• Medical history of positive serostatus for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) at any time before treatment:
• Positive anti-HIV-1 or anti-HIV-2 antibodies,
• or positive HBsAg
• or positive anti-HCV antibody or quantifiable HCV-RNA.
• For subjects with no previous result report, whether to conduct testing of serostatus during the screening period will be at the discretion of the investigator;
• Medical history (≤6 months before treatment) or evidence of any serious and/or uncontrolled medical condition or circumstances that the investigator and sponsor believe may affect the subject's participation in the study, for example:

Sponsors & Collaborators

• Jiangsu Chia Tai Fenghai Pharmaceutical Co., Ltd.: lead

Study Sites (2)

Shanghai Chest Hospital

Shanghai, China

Location

Tianjin People's Hospital

Tianjin, China

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2023
• First Posted: April 19, 2023
• Study Start: July 7, 2022
• Primary Completion: December 31, 2023
• Study Completion: July 31, 2024
• Last Updated: April 19, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)