A PARG Inhibitor DAT-2645 Monotherapy in Patients with Advanced/Metastatic Solid Tumors Harboring BRCA1/2 Loss of Function Alterations And/or Other Defects in the DDR Pathway

Danatlas Pharmaceuticals Co., Ltd

Status and phase: Not yet enrolling; Phase 1

Conditions: Advanced Cancer; Endometrial Cancer; Breast Cancer; BRCA Mutation; Gastric Cancer; Solid Cancers; Metastatic Solid Tumors; HRD Cancer; Prostate Cancer; Pancreatic Cancer; Colorectal Cancer

Treatments: Drug: DAT-2645 tablet

Study type: Interventional

Funder types: Industry

Identifiers

NCT06614751

Danatlas Pharmaceuticals Co.

Details and patient eligibility

About

The primary objective of the study is to evaluate the safety, tolerability, PK, PD, and prilimary efficacy of a PARG inhibitor DAT-2645 in patients with advanced/metastatic solid tumors harboring BRCA1/2 loss of function alterations and/or other defects in the DNA damage repair (DDR) pathway.

Full description

This the the FIH trial of PARG inhibitor DAT-2645.This study will include Part 1 dose escalation study and Part 2 dose expansion study. Eligible patients will be enrolled into Part 1 and Part 2.

In Part 1, 6 dose cohorts will be set and definte MTD/RDE. In Part 2, Dose optimization will be conducted firstly to definite RP2D. dose expansion will be conducted in another 2 cohorts to evaluate the efficacy.

Enrollment: 112 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Signed informed consent prior to initiation of any procedures in this study.
• At least 18 years of age (inclusive).
• Evidence of an DDR deficiency status in tumor tissue determined by validated testing method.
• Patients with advanced or metastatic solid tumor who have failed standard of care therapy, or are unable to tolerate standard of care therapy, or unable to obtain/unwilling to receive standard therapy. Regardless of PARP inhibitors were used or not in previous treatment.
• At least one measurable lesion by RECIST v1.1 criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0~2.
• Life expectancy at least 3 months.
• Adequate hematologic and non-hematologic function during the screening.
• Women of childbearing potential must have a negative result of serum pregnancy test at screening.
• Women of childbearing potential or male patients whose spouse have childbearing potential must agree to use a reliable and effective method of contraception during the study and for 6 months after the last dose of the study drug.

Exclusion criteria

• Patients who received systemic chemotherapy, small-molecule targeted drugs within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study drug.
• Patients who received biological anti-tumor drugs (including immunotherapy, target therapy, antibody-drug conjugate [ADC]) within 4 weeks prior to the first dose of the study drug.
• Patients who have undergone major surgery within 4 weeks prior to the first dose of study drug.
• Patients who have received radiotherapy within 4 weeks prior to the first dose of study drug (palliative radiotherapy for non-target lesions could be acceptable if it was performed before 14 days prior to the first dose of study drug).
• Any previous treatment with a PARG inhibitor.
• Patients with active CNS metastases (patients with asymptomatic CNS metastases which are imaging stable and not require steroid treatment within 28 days prior to the first dose of study drug, and previous treated breast cancer brain metastasis, can only be enrolled in the Part 2 study).
• Patients who have second primary malignant tumors within the past 3 years prior to screening, except for those who have been cured of basal cell carcinoma, cervical carcinoma in situ, or breast carcinoma in situ.
• Patients with clinically significant cardiovascular or cerebrovascular diseases.
• Active uncontrolled infections requiring intravenous antibiotics or hospitalization.
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of DAT-2645 and no history of bowel obstruction within 6 months prior to enrollment.
• Known pulmonary interstitial disease or pulmonary interstitial fibrosis.
• Patients known hypersensitivity to any component or excipient of DAT-2645.
• Any unresolved toxicities from any prior therapy with severity great than CTCAE Grade 1 prior to start of DAT-2645, except for alopecia and pigmentation and Grade 2 of peripheral sensory neuropathy.
• Participated in other clinical trials (except for screening failure) within 4 weeks prior to the first dose of the study drug in this study.
• Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (active HBV infection is defined as positive hepatitis B surface antigen [HbsAg], or HBV DNA exceeding the lower limit of detection; active HCV infection is defined as positive anti-HCV antibody, and HCV RNA exceeding the lower limit of detection).
• Known human immunodeficiency virus (HIV) infection (patients with adequate CD4+ T cell counts and without history of acquired immune deficiency syndrome [AIDS]-defining opportunistic infections could be enrolled after consultation with sponsor).
• Women who are pregnant or breastfeeding.
• History or evidence of any other clinically significant condition or disease (with the exception of those outlined above) that, in the opinion of the investigator, would be a risk to patient safety or interfere with the study evaluation, procedures or completion.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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112 participants in 3 patient groups

Part 1, Dose escalation

Experimental group

Description:

Monotherapy, dose escalation to definite MTD or RDE.

Treatment:

Drug: DAT-2645 tablet

Drug: DAT-2645 tablet

Module 1 Part 2, Dose optimizing

Experimental group

Description:

Dose optimizing by 2 dose level after dose escalation to definite RP2D

Treatment:

Drug: DAT-2645 tablet

Drug: DAT-2645 tablet

Module 2 Part 2, Dose expansion

Experimental group

Description:

To evaluate safety and efficacy of DAT-2645 tablet in solid tumor under RP2D dosage

Treatment:

Drug: DAT-2645 tablet

Drug: DAT-2645 tablet