Solid CancersPhase 1NCT06614751
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
A Phase 1 study testing DAT-2645 tablet in people with Solid Cancers and BRCA Mutation, run by Danatlas Pharmaceuticals Co., Ltd at 2 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Cancers, BRCA Mutation, HRD Cancer
- What is being tested?
- DAT-2645 tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 112 participants
- Where
- 2 sitesChina
- Study dates
- 1 Nov 2024to 1 Jun 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- 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.
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- 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.
Who cannot join
- 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).
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- 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 locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites
Peking University Cancer Hospital and Institute
Beijing, Beijing Municipality, 100048
Hong Zheng, MD, PhD, +86-13641356816, Zhhong306@Hotmail.com
Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Beijjing, Beijing Municipality, 100021
Binghe XU,, MD, PhD, +86-13501028690, xubinghe@medmail.com.cn
About this study
Official title: A Phase I, Open-label, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of 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 Pathway
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.
Read the detailed 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.
- Conditions
- Solid Cancers, BRCA Mutation, HRD Cancer, Breast Cancer, Prostate Cancer, Colorectal Cancer
- Being tested
- DAT-2645 tablet
- Keywords
- PARGi, DAT-2645, PARPi, Advanced solid tumors, Metastatic solid tumors, HRD gene alteration, Homologous recombination, BRCA, BRCA1/2, PALB2, RAD51C, RAD51D
- Medical subject headings
- Breast Neoplasms, Prostatic Neoplasms, Colorectal Neoplasms, Pancreatic Neoplasms, Endometrial Neoplasms, Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DAT-2645 tabletDrug
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.
DAT-2645 tabletDrug
The study set 6 dose level cohorts in dose escalation part.On C0D1, patient take DAT-2645 one time (Single use), The dosage is same as his enrolled cohort dose level. if no DLT, 7 days later(C1D1), patients will continue taking DAT-2645 tablet daily, dasage is same as before, 21days/cycle.
| Study group | Role | What they receive |
|---|---|---|
| Part 1, Dose escalation | Experimental | Monotherapy, dose escalation to definite MTD or RDE. Receives: Drug: DAT-2645 tablet |
| Module 1 Part 2, Dose optimizing | Experimental | Dose optimizing by 2 dose level after dose escalation to definite RP2D Receives: 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 Receives: Drug: DAT-2645 tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: Approximately 2 years
Secondary outcomes (11)
RP2D
Recommended Phase 2 dose, will be definite by safety mornitoring committe(SMC).
Measured: Approximately 6 months
ORR
Objective Response Rate (ORR) was calculated the rate of response of complete response (CR) or partial response (PR).
Measured: Average of 6 months
DCR
Defined as not meeting the criteria for progression and PR(partial response)
Measured: Average of 6 months
DoR
DoR(duration of response) per RECIST v1.1(Response Evaluation Criteria in Solid Tumours).
Measured in CT/MRI image from the time when measurement criteria for complete/ partial response are met till time when progression of the disease is documented.
Measured: Approximately 1 years
PFS
Progression- free survival (PFS) by RECIST V1.1 criteria- from the beginning of treatment to the progression of disease or death.
Measured: Approximately 2 years
OS
Overall Survival (OS) was defined as the time interval between a patient randomized and death from any cause or the end of the last follow-up date.
Measured: Approximately 2 years
Area Under the Plasma Concentration Versus Time Curve (AUC) of DAT-2645
PK parameters of DAT-2645 and metabolite over time at Cycle 0 Day 1 and at steady state (Cycle 1 Day 21) to model Area Under the the Plasma Concentration Versus Time Curve (AUC) with trough levels at the beginning of every Cycle thereafter
Measured: Approximately 1 years
Changes in lysate poly (ADP-ribose) (PAR) level
As a PD parameter, detect the PAR level in peripheral blood mononuclear cell (PBMC) before and after administration of DAT-2645. Explore the correlation between DAT-2645 exposure and PD parameter, safety events.
Measured: 6 months
Correlations between patients' baseline characteristics and effecacy
Correlations between patients' baseline characteristics (e.g., DDR deficiency type, tumor type) and objective response rate (ORR), to explore the best biomarker for tumor selection.
Measured: Approximately 2 years
Time to Achieve Maximal Plasma Concentration (Tmax) of DAT-2645 in Part 1 and Part 2
PK parameters of DAT-2645 and metabolite over time at Cycle 0 Day 1 and at steady state (Cycle 1 Day 21) to model time to maximum concentration (Tmax) with trough levels at the beginning of every Cycle thereafter
Measured: Approximately 1 years
Maximal Plasma Concentration (Cmax) of DAT-2645 in Part 1 and Part 2
PK parameters ofDAT-2645 and metabolite over time at Cycle 0 Day 1-Cycle 0 Day 6 and at steady state (Cycle 1 Day 21) to model maximum concentration (Cmax) with trough levels at the beginning of every Cycle thereafter
Measured: Approximately 1 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2024
- Study start1 Nov 2024 (estimated)
- Primary completion1 Nov 2026 (estimated)
- Study completion1 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid CancersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 112 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Danatlas Pharmaceuticals Co., Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06614751
- Sponsor's protocol ID
- Danatlas Pharmaceuticals Co.
- Status last verified
- Sep 2024
- First submitted
- 18 Sep 2024
- Last updated
- 27 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: only IPD used in the results publication
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-label, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of 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 Pathway
- ClinicalTrials.gov ID
- NCT06614751
- Acronym / sponsor ID
- Danatlas Pharmaceuticals Co.
- Conditions
- Solid Cancers, BRCA Mutation, HRD Cancer, Breast Cancer, Prostate Cancer, Colorectal Cancer
- Keywords
- PARGi, DAT-2645, PARPi, Advanced solid tumors, Metastatic solid tumors, HRD gene alteration, Homologous recombination, BRCA
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 112 participants (estimated)
- Lead sponsor
- Danatlas Pharmaceuticals Co., LtdIndustry (pharma, biotech, devices)
- Study start
- 1 Nov 2024 (estimated)
- Primary completion
- 1 Nov 2026 (estimated)
- Study completion
- 1 Jun 2027 (estimated)
- First posted
- 26 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part 1, Dose escalation | Experimental | Drug: DAT-2645 tabletMonotherapy, dose escalation to definite MTD or RDE. |
| Module 1 Part 2, Dose optimizing | Experimental | Drug: DAT-2645 tabletDose optimizing by 2 dose level after dose escalation to definite RP2D |
| Module 2 Part 2, Dose expansion | Experimental | Drug: DAT-2645 tabletTo evaluate safety and efficacy of DAT-2645 tablet in solid tumor under RP2D dosage |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DAT-2645 tabletThe 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. | Drug | Module 1 Part 2, Dose optimizing, Module 2 Part 2, Dose expansion |
| DAT-2645 tabletThe study set 6 dose level cohorts in dose escalation part.On C0D1, patient take DAT-2645 one time (Single use), The dosage is same as his enrolled cohort dose level. if no DLT, 7 days later(C1D1), patients will continue taking DAT-2645 tablet daily, dasage is same as before, 21days/cycle. | Drug | Part 1, Dose escalation |
Primary outcome
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
Time frame: 6 months
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
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
Time frame: Approximately 2 years
Tumor response: Overall Response Rate(ORR) assessed by the investigators based on RECIST v1.1 criteria
11 secondary outcomes
RP2D
Time frame: Approximately 6 months
ORR
Time frame: Average of 6 months
DCR
Time frame: Average of 6 months
DoR
Time frame: Approximately 1 years
PFS
Time frame: Approximately 2 years
OS
Time frame: Approximately 2 years
Area Under the Plasma Concentration Versus Time Curve (AUC) of DAT-2645
Time frame: Approximately 1 years
Changes in lysate poly (ADP-ribose) (PAR) level
Time frame: 6 months
Correlations between patients' baseline characteristics and effecacy
Time frame: Approximately 2 years
Time to Achieve Maximal Plasma Concentration (Tmax) of DAT-2645 in Part 1 and Part 2
Time frame: Approximately 1 years
Maximal Plasma Concentration (Cmax) of DAT-2645 in Part 1 and Part 2
Time frame: Approximately 1 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2024.
- Individual participant dataSharing planned: Yes. only IPD used in the results publication
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DAT-2645 tablet in people with Solid Cancers and BRCA Mutation, run by Danatlas Pharmaceuticals Co., Ltd at 2 sites 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 10 inclusion and 18 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: opening soon, as of the sponsor's last update on 27 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Danatlas Pharmaceuticals Co. (+86-18911453323, information@danatlas.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: 6 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?
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 27 Sep 2024.