An Phase Ib/II Clinical Trial of TCC1727 Combination Therapy in Advanced Solid Tumors

NCT07371663 | Recruiting Phase 1

• 1 other identifier: TCC1727-II-01
• Study Type: interventional
• Target: 266
• Locations: 1 country
• Sites: 3

Brief Summary

This is a Phase Ib/II clinical study. The Phase Ib dose-escalation study aims to evaluate and determine the recommended Phase II dose (RP2D) of TCC1727 in combination with benmelstobart /olaparib /topotecanfor patients with advanced solid tumors. The Phase II expansion study will assess the efficacy and safety of TCC1727 combined with benmelstobart /olaparib/topotecanin selected advanced solid tumor indications. The study pre-specifies three treatment combinations, with Combination 1 (TCC1727 + benmelstobart) being prioritized for initial evaluation. The decision to proceed with Combination 2 and Combination 3will be based on clinical data from Combination 1.

Conditions

Solid Cancers; NSCLC (Advanced Non-small Cell Lung Cancer); Gastric (Stomach) Cancer; Endometrial Cancer; Malignant Melanoma

Keywords

Ataxia Telangiectasia and Rad3-related protein inhibitor; Advanced solid tumor

Outcome Measures

Primary Outcomes (4)

• Phase Ib：To determine dose-limiting toxicity (DLT) at each dose level

  Dose Escalation To observe the tolerability and safety of TCC1727 combination therapy.

  21 Days

• MTD

  The maximum tolerated dose (MTD) of TCC1727 in combination with benmelstobart/olaparib/topotecan will be determined based on safety, tolerability, kinetics, preliminary efficacy, and other available data

  21 days

• RP2D

  The recommended Phase II dose (RP2D) of TCC1727 in combination with benmelstobart/olaparib/topotecan will be determined based on safety, tolerability, kinetics, preliminary efficacy, and other available data

  21 days

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  Adverse events (AEs) were assessed according to NCI-CTCAE v5.0, including severity grading of abnormal findings in laboratory tests, vital signs, physical examinations, and electrocardiograms (ECGs) from signing of informed consent through the end of the safety follow-up period or prior to the start of a new anticancer therapy

  21days

Secondary Outcomes (14)

• Assess objective response rate (ORR: complete response + partial response), based on RECIST 1.1

  6 month

• PK parameters of TCC1727

  Day1, Day22

• PK parameters of TCC1727

  Day1, Day22

• PK parameters of TCC1727

  Day1, Day22

• AUC0-t

  Day1, Day22

Other Outcomes (3)

• Baseline tumor tissue predictive biomarkers

  Screening visit（Day-28 to Day1）

• Correlation between mutation status of DDR-related genes in baseline tumor tissues and efficacy of TCC1727 combination therapy

  Screening visit（Day-28 to Day1）

• Before and after treatment, the distribution changes of blood immune cells . (only applicable to the combination with Benmelstobart)

  Screening visit（Day-28 to Day1）, Cycle1Day8, Cycle1Day15, Cycle2Day1(Each cycle is 21days)

Study Arms (3)

TCC1727 + benmelstobart (Dose Level 1)

EXPERIMENTAL

TCC1727 tablets 90 mg orally twice daily (bid) in 21-day cycles combined with benmelstobart injection 1200 mg by intravenous infusion in 21-day cycles until disease progression

Drug: TCC1727 tablet 90mg; Combination Product: benmelstobart Injection

TCC1727 + benmelstobart (Dose Level 2)

EXPERIMENTAL

TCC1727 tablets 120 mg orally twice daily (bid) in 21-day cycles combined with benmelstobart injection 1200 mg by intravenous infusion in 21-day cycles until disease progression

Drug: TCC1727 tablet 120mg; Combination Product: benmelstobart Injection

TCC1727 + benmelstobart (Dose Level 3)

EXPERIMENTAL

TCC1727 tablets 160 mg orally twice daily (bid) in 21-day cycles combined with benmelstobart injection 1200 mg by intravenous infusion in 21-day cycles until disease progression

Drug: TCC1727 tablet 160mg; Combination Product: benmelstobart Injection

Interventions

TCC1727 tablet 90mg DRUG

TCC1727 tablets 90 mg, orally, twice daily (bid), continuous dosing in 21-day cycles until disease progression

TCC1727 + benmelstobart (Dose Level 1)

TCC1727 tablet 120mg DRUG

TCC1727 tablets 120 mg, orally, twice daily (bid), continuous dosing in 21-day cycles until disease progression

TCC1727 + benmelstobart (Dose Level 2)

TCC1727 tablet 160mg DRUG

TCC1727 tablets 160 mg, orally, twice daily (bid), continuous dosing in 21-day cycles until disease progression

TCC1727 + benmelstobart (Dose Level 3)

benmelstobart Injection COMBINATION_PRODUCT

Administer 1200 mg per dose via intravenous infusion on Day 1 of every 3-week cycle until disease progression.

TCC1727 + benmelstobart (Dose Level 1); TCC1727 + benmelstobart (Dose Level 2); TCC1727 + benmelstobart (Dose Level 3)

Eligibility Criteria

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

You may qualify if:

• Voluntarily participate in this study and sign the informed consent form.
• At the time of signing the informed consent, subjects must be ≥18 years of age (inclusive).
• Subjects must have histologically or cytologically confirmed advanced or metastatic solid tumors and have experienced disease progression following prior standard anti-tumor therapy; or subjects must have no available standard therapy, be intolerant to or refuse standard therapy, or meet the specific requirements for the corresponding phase and group as follows:
• Phase Ib :Subjects with advanced, recurrent, or refractory solid tumors, which may include (but are not limited to) the specific tumor types in Phase II.
• Phase II Study:Based on different combination therapy groups, subjects with the following specific tumor types (different population cohorts):
• TCC1727 combined with Benmelstobart Group:
• The study will enroll subjects with advanced solid tumors lacking standard therapies, including but not limited to non-small cell lung cancer (NSCLC), endometrial cancer, and other advanced solid tumors (e.g., colorectal cancer, urothelial carcinoma, gastric cancer, and gastroesophageal junction cancer):
• Cohort 1 (NSCLC):Patients with histologically or cytologically confirmed locally advanced or metastatic NSCLC who are eligible for second- or third-line therapy. Patients must have received prior therapy with an anti-PD-(L)1-containing regimen (either as monotherapy or in combination) and a platinum-based doublet regimen for locally advanced or metastatic NSCLC.
• Subgroup 1: ATM mutation. Subgroup 2: ATM wild-type, with or without other DDR functional defects.
• Cohort 2 (Endometrial Cancer):Patients with histopathologically confirmed recurrent or metastatic advanced endometrial cancer who have received at least one prior platinum-based chemotherapy and immune checkpoint inhibitor (PD-1 or PD-L1) therapy (sequential or concurrent therapy allowed; sequential therapy refers to platinum-based chemotherapy followed by immune checkpoint inhibitor maintenance therapy).
• Subgroup 1: DDR functional defect, ATM wild-type or mutated. Subgroup 2: DDR functional normal.
• Cohort 3 (Other Advanced Solid Tumors):Patients with histologically or cytologically confirmed advanced malignant solid tumors who have failed standard therapy, are intolerant to standard therapy, have no standard therapy available, or for whom standard therapy is currently unsuitable.
• Subgroup 1: DDR functional defect, ATM wild-type or mutated. Subgroup 2: DDR functional normal.
• TCC1727 combined with Olaparib Tablets Group:
• The study will enroll subjects with histopathologically confirmed recurrent ovarian cancer:

You may not qualify if:

• Known primary central nervous system (CNS) tumors (including meningeal tumors); symptomatic brain metastases, spinal cord compression, carcinomatous meningitis, or uncontrolled CNS metastases. Exceptions: Subjects with completely resected and/or irradiated CNS metastases that are stable or improved for ≥4 weeks before screening (no evidence of brain edema and no need for corticosteroids or anticonvulsants). Asymptomatic brain metastases \<1 cm in diameter without surrounding edema are also allowed.
• Major surgery, radiotherapy, chemotherapy, or other investigational anti-tumor therapy completed \<4 weeks before the first dose (exceptions: small-molecule anti-tumor therapy completed \>5 half-lives or \>10 days before the first dose, whichever is longer; palliative radiotherapy completed \>2 weeks before the first dose).
• Use of strong CYP3A4 inhibitors or inducers within 14 days before the first dose (e.g., rifampin, rifapentine, St. John's wort, carbamazepine, phenytoin, barbiturates, ketoconazole, itraconazole, clarithromycin, voriconazole, atazanavir, ritonavir, saquinavir, grapefruit juice).
• Inability to swallow tablets, gastrointestinal dysfunction, or any condition that may affect drug absorption (per investigator's judgment).
• Uncontrolled severe diseases, including:
• Poorly controlled hypertension (systolic BP ≥150 mmHg or diastolic BP ≥100 mmHg);
• Clinically significant cardiovascular disease within 6 months before the first dose (e.g., myocardial infarction, severe/unstable angina, stroke, ≥Grade 2 congestive heart failure \[NYHA classification\]);
• Arrhythmia (≥Grade 2 per CTCAE v5.0, including QTcF ≥450 ms \[male\] or ≥470 ms \[female\]);
• Unexplained fever ≥38.5°C within 14 days before the first dose or active infection requiring systemic therapy;
• Active viral hepatitis (HBV DNA ≥500 IU/mL for HBsAg-positive and/or anti-HBc-positive subjects; HCV RNA-positive for anti-HCV-positive subjects; antiviral therapy required for eligible HBV/HCV-positive subjects);
• Active syphilis;
• Active tuberculosis;
• Immunodeficiency (e.g., HIV-positive, congenital/acquired immunodeficiency, organ transplant history);
• Poorly controlled diabetes (fasting blood glucose \>10 mmol/L).
• Uncontrolled pleural effusion, pericardial effusion, ascites, or recurrent ascites requiring drainage within 28 days before the first dose.

Sponsors & Collaborators

• Beijing Tide Pharmaceutical Co., Ltd: lead

Study Sites (3)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

NOT YET RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

NOT YET RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Stomach Neoplasms; Endometrial Neoplasms; Melanoma; Ataxia Telangiectasia

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Spinocerebellar Ataxias; Cerebellar Ataxia; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocutaneous Syndromes; Ataxia; Dyskinesias; Neurologic Manifestations; Telangiectasis; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Primary Immunodeficiency Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Central Study Contacts

Zhengbo Song

CONTACT

+86 13857153345; songzb@zjcc.org.cn

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: December 15, 2025
• First Posted: January 28, 2026
• Study Start: December 3, 2025
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: January 28, 2026

Record last verified: 2025-10

Locations

CN (3)