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

NCT06614751 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: Danatlas Pharmaceuticals Co.
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

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

Keywords

PARGi; DAT-2645; PARPi; Advanced solid tumors; Metastatic solid tumors; HRD gene alteration; Homologous recombination; BRCA; BRCA1/2; PALB2; RAD51C; RAD51D

Outcome Measures

Primary Outcomes (2)

• Part 1, Dose esclalation study:To characterize the safety and tolerability of DAT-2645 monotherapy by evaluating the number of participants with dose limiting toxicities, adverse events, and laboratory abnormalities as graded by NCI CTCAE version 5.0

  The incidence of dose limiting toxicites Incidence of treatment-emergent Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing

  6 months

• Part 2, Dose expansion study: To evaluate preliminary preliminary anti-tumor activity of DAT-2645 tablet monotherapy in participants by measuring tumor Overall Response Rate using RECIST criteria v1.1

  Tumor response: Overall Response Rate(ORR) assessed by the investigators based on RECIST v1.1 criteria

  Approximately 2 years

Secondary Outcomes (11)

• RP2D

  Approximately 6 months

• ORR

  Average of 6 months

• DCR

  Average of 6 months

• DoR

  Approximately 1 years

• PFS

  Approximately 2 years

Study Arms (3)

Part 1, Dose escalation

EXPERIMENTAL

Monotherapy, dose escalation to definite MTD or RDE.

Drug: DAT-2645 tablet

Module 1 Part 2, Dose optimizing

EXPERIMENTAL

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

Drug: DAT-2645 tablet

Module 2 Part 2, Dose expansion

EXPERIMENTAL

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

Drug: DAT-2645 tablet

Interventions

DAT-2645 tablet DRUG

The patient will be randomized into 2 groups and take DAT-2645 tablet daily. dosage is optimal dose-1 or optimal dose-2, 21day/ Cycle. The subject of this part is to optimize dosage and definite RP2D.

Module 1 Part 2, Dose optimizing; Module 2 Part 2, Dose expansion

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Danatlas Pharmaceuticals Co., Ltd: lead

Study Sites (2)

Peking University Cancer Hospital and Institute

Beijing, Beijing Municipality, 100048, China

Location

Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Beijjing, Beijing Municipality, 100021, China

Location

MeSH Terms

Conditions

Breast Neoplasms; Prostatic Neoplasms; Colorectal Neoplasms; Pancreatic Neoplasms; Endometrial Neoplasms; Stomach Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Stomach Diseases

Central Study Contacts

Danatlas Pharmaceuticals Co.

CONTACT

+86-18911453323; information@danatlas.com

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: September 18, 2024
• First Posted: September 26, 2024
• Study Start: November 1, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: September 27, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Danatlas will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please contact with us by information@danatlas.com.
• Access Criteria: When a request has been approved Danatlas will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.Please contact with sponsor by email information@danatlas.com

Locations

CN (2)