A Phase I/II Clinical Study in Patients with Advanced Solid Tumor.

NCT05970016 | Recruiting Phase 1

• 1 other identifier: TCC1727-101
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

This is a 2-part, phase I/II, open-label, multicenter study designed to evaluate the safety, PK, PD and preliminary efficacy of TCC1727 tablets administered orally QD.

Conditions

Patients with Advanced Solid Tumors

Outcome Measures

Primary Outcomes (2)

• Phase I: To determine dose-limiting toxicity (DLT) at each dose level and identify MTD and RP2D.

  Phase I: Dose Escalation To observe the tolerability and safety of TCC1727 tablets and determine the maximum-tolerated dose (MTD) and the recommended phase II dose (RP2D) of TCC1727 tablets when administered orally once a day (QD) in 21-day cycle in patients with advanced solid tumors.

  21 days

• Phase II: To evaluate the preliminary efficacy of TCC1727 tablets as measured by ORR in patients with advanced solid tumors with DNA damage response (DDR) defects

  Phase II: Cohort Expansion ORR according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1, 2009) for each tumor type. The overall response rate is defined as proportion of subjects who had the best overall response (BOR) of complete response (CR) or partial response (PR).

  6 months

Secondary Outcomes (9)

• Phase I: Dose Escalation To observe the preliminary efficacy of TCC1727 tablets as measured by overall response rate (ORR) in patients with advanced solid tumors.

  6 months

• Phase I: To evaluate the pharmacokinetic (PK) of TCC1727 tablets in patients with advanced solid tumors

  21 days

• Phase I:

  21 days

• Phase I:

  21 days

• Phase I:

  21 days

Study Arms (11)

5mg treatment group

EXPERIMENTAL

Administered orally once a day (QD)

Drug: TCC1727 tablet（1）

10mg treatment group

EXPERIMENTAL

Administered orally once a day (QD)

Drug: TCC1727 tablet（1）

20mg treatment group

EXPERIMENTAL

Administered orally once a day (QD)

Drug: TCC1727 tablet（1）

40mg treatment group

EXPERIMENTAL

Administered orally once a day (QD)

Drug: TCC1727 tablet（1）

60mg treatment group

EXPERIMENTAL

Administered orally once a day (QD)

Drug: TCC1727 tablet（1）

80mg treatment group

EXPERIMENTAL

Administered orally once a day (QD)

Drug: TCC1727 tablet（1）

100mg treatment group

EXPERIMENTAL

Administered orally once a day (QD)

Drug: TCC1727 tablet（1）

60mg BID treatment group

EXPERIMENTAL

Drug: TCC1727 tablet TCC1727 tablet will be administered orally twice a day (BID) every morning , and 21 days/cycle on an empty stomach.

Drug: TCC1727 tablet（2）

90mg BID treatment group

EXPERIMENTAL

Drug: TCC1727 tablet TCC1727 tablet will be administered orally twice a day (BID) every morning, and 21 days/cycle on an empty stomach.

Drug: TCC1727 tablet（2）

120mg BID treatment group

EXPERIMENTAL

Drug: TCC1727 tablet TCC1727 tablet will be administered orally twice a day (BID) every morning, and 21 days/cycle on an empty stomach.

Drug: TCC1727 tablet（2）

160mg BID treatment group

EXPERIMENTAL

Drug: TCC1727 tablet TCC1727 tablet will be administered orally twice a day (BID) every morning, and 21 days/cycle on an empty stomach.

Drug: TCC1727 tablet（2）

Interventions

TCC1727 tablet（1） DRUG

TCC1727 tablet will be administered orally once a day (QD) every morning for 3 days followed by discontinuation for 4 days, and 21 days/cycle on an empty stomach.

100mg treatment group; 10mg treatment group; 20mg treatment group; 40mg treatment group; 5mg treatment group; 60mg treatment group; 80mg treatment group

TCC1727 tablet（2） DRUG

Drug: TCC1727 tablet TCC1727 tablet will be administered orally twice a day (BID) every morning , and 21 days/cycle on an empty stomach.

120mg BID treatment group; 160mg BID treatment group; 60mg BID treatment group; 90mg BID treatment group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects who have provided voluntary informed consent for participation in the study and to follow the protocol requirements
• Male or female subjects 18-70 years of age
• Subjects with histologically or cytologically confirmed malignant advanced solid tumors who have progressed on (or have not been able to tolerate) standard therapy or for whom no suitable effective standard therapy exists
• For Phase I, all tumor types will be enrolled
• For Phase II, Patients with DDR defects detection at central laboratory will be enrolled
• Subject with at least one measurable lesion according to RECIST criteria (version 1.1) for solid tumors will be allowed to include in phase II (if there is no measurable lesion but there are assessable lesions then the subject will be allowed to be included after the judgment of the investigator in phase I only)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Subjects with life expectancy of ≥12 weeks
• Subjects 12-lead ECG evaluation of QT level using Fridericia formula (QTcF) \< 450 mse
• Subjects must have the following laboratory values:
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L;
• Platelet count (PLT) ≥ 100 × 109/L;
• Hemoglobin (HB) ≥ 9.0 g/L;
• No blood transfusion or hematopoietic stimulating factor treatment within 14 days;
• Bilirubin total ≤ 1.5 times the upper limit of normal (ULN);

You may not qualify if:

• Subjects will be excluded from the study based on the following criteria:
• History of previously received major surgery or surgical therapy for any cause within 4 weeks of the first dose; radiotherapy, chemotherapy, other clinical trial drugs or other anti-tumor treatment, within 5 half-lives or 3 weeks (whichever is shorter), prior administering the first dose of study drug on Day 1
• History of previous treatment with ATR inhibitors or other DDR related inhibitors (except poly ADP ribose polymerase enzyme (PARP) inhibitors)
• Subjects with a history of another primary malignancy other than:
• carcinomas in situ, (e.g., breast, cervix, and prostate)
• Locally excised non-melanoma skin cancer
• No evidence of disease from another primary cancer for two or more years and has not taken any anti-cancer treatment in two years. Exceptions are gonadotropin-releasing hormone (GnRH) therapy for prostate cancer and hormonal maintenance therapy for breast cancer.
• Previously received treatment with strong CYP3A4, CYP2C8 and P-gp inhibitors or strong CYP3A4, CYP2C8 and P-gp inducers within 14 days prior to the first medication
• Patients with AE due to previous anti-tumor treatment that has not recovered to ≤ CTCAE grade 1 (except for alopecia, pigmentation and lymphopenia)
• Patients who are unable to swallow the tablets normally, or have abnormal gastrointestinal function that may affect the drug absorption, such as malabsorption syndrome or major resection of the stomach or bowels based on the judgment of the investigator
• Subjects with any severe and/or uncontrolled disease, including:
• Poor blood pressure control (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg)
• Myocardial infarction, arrhythmia (CTCAE grade 2 and above, also including ≥ Class II congestive heart failure (CHF) (New York Heart Association (NYHA) classification) (refer to Appendix-A)
• Active infection or fever of unknown origin ≥ 38.5℃ within 7 days prior to the first medication
• Active viral hepatitis; positive hepatitis B surface antigen and/or hepatitis B core antibody and measured HBV DNA value ≥ 500 IU/ml; positive HCV antibody and measured HCV titer exceeding the upper limit of normal;

Sponsors & Collaborators

• Beijing Tide Pharmaceutical Co., Ltd: lead

Study Sites (1)

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100000, China

RECRUITING

Central Study Contacts

Lingying Wu, PHD

CONTACT

86-01-87788996; wulingying@csco.org.cn

Guangwen Yuan, PHD

CONTACT

86-01-87788996; william327@126.com

Study Design

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

Study Record Dates

• First Submitted: July 14, 2023
• First Posted: August 1, 2023
• Study Start: August 7, 2023
• Primary Completion: July 30, 2025
• Study Completion: December 30, 2025
• Last Updated: March 21, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)