GenSci145 as Monotherapy or in Combination Therapy, in Participants With PIK3CA-mutated, Locally Advanced or Metastatic Solid Tumors.

Recruiting now · Phase 1

Conditions studied: Locally Advanced or Metastatic Solid Tumors With PIK3CA-mutated

In brief

An international, multicenter, open-label, Phase 1/2 clinical study to evaluate the safety, tolerability, pharmacokinetic characteristics, and efficacy of GenSci145, as monotherapy or in combination therapy, in participants with PIK3CA-mutated, locally advanced or metastatic solid tumors.

Key facts

Study ID

NCT07407504

Run by

Changchun GeneScience Pharmaceutical Co., Ltd.

People needed

186

Starts

2026-04-01

Expected to finish

2029-02-21

Last updated by the study team

2026-05-27

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Ability to understand and voluntarily provide written ICF.
• Willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other protocol-specified procedures.
• Age 18-75 years (inclusive) at the time of providing informed consent.
• Disease diagnosis requirements:
• Part 1:
• Histologically or cytologically confirmed locally advanced or metastatic solid tumors.
• Disease progression after standard therapy, or, in the opinion of the investigator, no available and effective standard therapy.
• Part 2:
• Histologically or cytologically confirmed HR+/HER2- locally advanced or metastatic breast cancer [HR+ is defined as estrogen receptor (ER) positive and/or progesterone receptor (PR) positive (≥10% of tumor cell nuclei showing positive staining); HER2- is defined as immunohistochemistry (IHC) 0 or 1+, or IHC 2+ with a negative in situ hybridization (ISH) result].
• Disease progression after standard therapy, or, in the opinion of the investigator, no available and effective standard therapy.
• Part 3 (doublet) and Part 4 Cohort 1:
• Histologically or cytologically confirmed HR+/HER2- locally advanced or metastatic breast cancer.
• Patients must meet one of the following:
• Disease progression during (neo)adjuvant endocrine therapy or within 12 months after completion of such therapy, without having received any prior therapy for metastatic disease.
• Disease progression occurring more than 12 months after completion of adjuvant endocrine therapy, followed by first-line endocrine therapy for metastatic disease, with subsequent progression on that therapy.
• Newly diagnosed advanced breast cancer with progression after first-line endocrine therapy.
• Received ≤1 line of chemotherapy for advanced disease.
• Prior use of CDK4/6 inhibitors must meet one of the following:
• Received CDK4/6 inhibitor therapy in the advanced setting with disease progression occurring during or within 12 months after treatment.
• Discontinued treatment due to intolerability caused by adverse reactions (e.g., hyperglycemia, rash).
• If not previously treated with a CDK4/6 inhibitor, a reasonable explanation must be provided (e.g., lack of drug availability).
• Part 3 (triplet) and Part 4 Cohort 3:
• Histologically or cytologically confirmed HR+/HER2- locally advanced or metastatic breast cancer.
• Disease progression during adjuvant endocrine therapy with an aromatase inhibitor or tamoxifen, or within 12 months after completion of adjuvant endocrine therapy. If a CDK4/6 inhibitor was included as part of the (neo)adjuvant therapy, disease progression must occur >12 months after completion of CDK4/6 inhibitor therapy.
• Part 4 Cohort 2:

You may not qualify if…

• History of any active malignancy within ≤2 years prior to the first dose of GenSci145, except for the malignancy under investigation in this study and any curatively treated locally recurrent malignancies
• Presence of symptomatic, untreated, or progressing CNS metastases. Participants with previously treated CNS metastases (e.g., by surgery or radiotherapy) are eligible only if all of the following conditions are met:
• Disease stable for at least 3 months, with no evidence of progression on imaging within 4 weeks prior to first dose of study treatment, all neurologic symptoms recovered to baseline, and no evidence of new or enlarging brain metastases.
• At least 4 weeks have elapsed since completion of CNS-directed radiotherapy, surgery, or corticosteroid therapy prior to the first dose of study treatment.
• History of leptomeningeal metastases, spinal cord compression, or leptomeningeal disease.
• History of acute pancreatitis (within 1 year) or chronic pancreatitis, or radiologic evidence of pancreatic metastases.
• History of stroke, transient ischemic attack, or other clinically significant cerebrovascular events within 6 months prior to the first dose of GenSci145.
• Active infection requiring intravenous antibiotics, or other uncontrolled intercurrent illness requiring hospitalization. Minor infections such as periodontal infection or urinary tract infection manageable with short-course oral antibiotics are permitted.
• Confirmed diagnosis of uncontrolled diabetes mellitus, defined as HbA1c ≥8% and/or fasting plasma glucose ≥140 mg/dL (7.7 mmol/L).
• Uncontrolled hypertension, defined as blood pressure ≥150/90 mmHg despite optimal medical management.
• Clinically significant cardiovascular disease, including but not limited to:
• Myocardial infarction or unstable angina within 6 months prior to the first dose of GenSci145.
• New York Heart Association (NYHA) Class III or higher within 4 weeks prior to the first dose.
• Left ventricular ejection fraction (LVEF) <50%, assessed by echocardiogram within 4 weeks prior to the first dose.
• Based on three consecutive resting ECGs collected during the screening, the average QT interval corrected by Fridericia's formula (QTcF) is >450 ms for males and >470 ms for females.
• Any condition associated with increased risk of torsades de pointes (e.g., persistent hypokalemia despite standard treatment, family
• history of long QT syndrome).
• Any clinically significant cardiac rhythm, conduction, or resting ECG abnormality (e.g., complete left bundle branch block, second- or third-degree atrioventricular block).
• Interstitial lung disease, drug-induced pneumonitis, radiation pneumonitis requiring corticosteroid treatment, or other severe pulmonary diseases affecting lung function.
• Gastrointestinal disorders that, in the opinion of the investigator, may interfere with the absorption of oral GenSci145, such as peptic ulcer disease, uncontrolled nausea or vomiting, malabsorption syndrome, history of small bowel resection, or active inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis).
• Uncontrolled serosal effusion, including pleural effusion, ascites, or pericardial effusion (participants with effusions that are controlled and stable for ≥2 weeks after treatment may be eligible).
• Prior treatment with PI3K, mTOR, or AKT inhibitors.
• Prior treatment with fulvestrant (except in Phase 1a and Part 4 Cohort 4).
• Receipt of a live attenuated vaccine within 4 weeks prior to the first dose of GenSci145.
• Prior anticancer therapies before the first dose of GenSci145 as follows:

Where it is running

• The Cancer Hospital of the Chinese Academy of Medical Sciences — Beijing, Beijing Municipality, China (enrolling)

Full record on ClinicalTrials.gov

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