A Phase l Study of By101921, an Oral PARP7 Inhibitor, in Patients With Advanced Solid Tumors

NCT06433726 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: BY1921-I-01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

BY101921 is a novel small molecule, being developed as a PARP7 inhibitor which acts on the PARP7 catalytic subunit, for the treatment of solid tumors. PARP7 is a member of the monoPARP family and involved in various biological processes such as gene expression, protein degradation, and cellular stress response. The results of non-clinical studies showed BY101921 was a potent inhibitor of PARP7 and had good selectivity. The primary objective is to assess the safety and tolerability and MTD of BY101921 in patients with refractory or metastatic solid tumors. This study will also evaluate pharmacokinetic (PK) profile, preliminary anti-tumor activity, major metabolites and biomarkers in patients with refractory or metastatic solid tumors.

Conditions

Solid Tumor, Adult

Outcome Measures

Primary Outcomes (2)

• To assess the safety and tolerability of BY101921 in patients with advanced solid tumors

  Grade and frequency of adverse events and serious adverse events

  through study completion (an average of 1.5 years)

• To assess the maximum tolerated dose (MTD)

  Incidence of Dose limiting Toxicities (DLTs)

  through study completion (an average of 1.5 years)

Secondary Outcomes (4)

• To assess preliminary antitumor activity of BY101921 in patients with advanced solid tumors

  through study completion (an average of 1.5 years)

• To assess pharmacokinetics (PK) parameters of BY101921 in patients with advanced solid tumors

  through study completion (an average of 1.5 years)

• To assess pharmacokinetics (PK) parameters of BY101921 in patients with advanced solid tumors

  through study completion (an average of 1.5 years)

• To assess pharmacokinetics (PK) parameters of BY101921 in patients with advanced solid tumors

  through study completion (an average of 1.5 years)

Study Arms (1)

BY101921

EXPERIMENTAL

Dose Escalation: Multiple doses of BY101921 for oral administration

Drug: BY101921 tablets

Interventions

BY101921 tablets DRUG

An oral PARP7 Inhibitor

BY101921

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients ≥18 years and ≤75 years of age.
• patients histologically or cytologically diagnosed advanced malignant solid tumors who have failed, cannot tolerate, or refuse prior standard treatment regimens. At least 1 measurable lesion per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
• Have a projected life expectancy of at least 3 months.
• Eastern Cooperative Oncology Group Performance Status 0 or 1.
• Adequate organ and bone marrow function. Laboratory tests that meet the following criteria within 7 days prior to the first dose of study treatment (without blood transfusion, erythropoietin, recombinant human thrombopoietin or colony stimulating factor therapy, renal replacement therapy, etc., within 28 days prior to the screening examination):
• Routine blood test:
• Absolute neutrophil count (ANC) ≥ 1.5×109/L Platelets count (PLT) ≥ 100×109/L Hemoglobin (Hb) ≥ 90 g/L
• Hepatic function:
• Total bilirubin (TBIL) ≤ 1.5×ULN Aspartate aminotransferase (AST) ≤ 2.5×ULN Alanine aminotransferase (ALT) ≤ 2.5×ULN ALT and AST ≤ 5×ULN and TBIL ≤ 3×ULN for patients with primary liver cancer, liver metastases, or Gilbert 's syndrome.
• Renal function:
• Creatinine clearance ≥ 50 mL/min (calculated according to Cockcroft-Gault formula).
• Coagulation function:
• International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5×ULN
• Females and males of childbearing potential must agree to use appropriate methods of contraception (hormonal/barrier method or abstinence) during the study and for 3 months after the last dose. Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days prior to administration.
• Understand and be willing to sign written informed consent and be able to follow the study protocol for treatment, visits, and other study procedures.

You may not qualify if:

• Previously treated with PARP-7 inhibitors.
• Treated with a potent CYP3A4 inhibitor or inducer within 2 weeks prior to the first dose of study treatment.
• Previous any treatment with of the following:
• Systemic chemotherapy, other antitumor agents (including endocrine therapy, macromolecular targeted therapy, immunotherapy, or biotherapy) within 4 weeks or 5 half-lives prior to the first dose of study treatment, or who need to continue receiving these agents during the study period;
• Small molecule targeted therapy within 2 weeks or 5 half-lives prior to the first dose of study treatment;
• Anti-tumor traditional Chinese medicine or proprietary Chinese medicine preparations prior to the first dose of study treatment;
• Nitrosourea or mitomycin C within 6 weeks prior to the first dose of study treatment;
• Palliative radiation therapy within 2 weeks prior to the first dose of study treatment;
• Investigational drug within 4 weeks prior to the first dose of study treatment; g Radical radiation therapy within 4 weeks prior to the first dose of study treatment.
• Major surgical intervention (excluding needle biopsy) within 28 days before study drug administration, surgical wound has not fully healed or surgery is scheduled during the study period.
• Brain metastasis (except asymptomatic, stable for more than 4 weeks prior to the first dose and not requiring steroid therapy for at least 4 weeks prior to the first dose, no imaging findings of marked edema around the tumor lesion), presence of meningeal metastasis or brainstem metastasis, or presence of spinal cord compression.
• History of other malignancy within the past 5 years, except skin basal cell carcinoma, skin squamous cell carcinoma, cervical carcinoma in situ, or other carcinomas in situ which have undergone curative treatment and have had no recurrence within 5 years after treatment.
• Toxicities from prior antitumor therapy that have not recovered to CTCAE version 5.0 Grade 1 or less, except CTCAE (V5.0) Grade 2 peripheral neurotoxicity and alopecia of any grade.
• Difficult-to-control pleural effusion, ascites, or pericardial effusion.etc, requiring repeated drainage and considered unsuitable for study enrollment by the investigator.
• Serious or uncontrolled diseases as assessed by the investigator, including but not limited to:

Sponsors & Collaborators

• Chengdu Baiyu Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Cancer Hospital Affiliated to Shandong First Medical University / Shandong Cancer Research Institute / Shandong Cancer Hospital

Jinan, Shandong, 250117, China

RECRUITING

Central Study Contacts

Jinming Yu

CONTACT

+8613806406293; 13370582181@163.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: May 13, 2024
• First Posted: May 30, 2024
• Study Start: March 11, 2024
• Primary Completion: June 30, 2025
• Study Completion: December 31, 2025
• Last Updated: May 30, 2024

Record last verified: 2024-05

Locations

CN (1)