hec169096 in participants with advanced solid tumors

Conditions: Advanced Solid Tumor

Summary: an open, multi-center phase i/ii clinical study to evaluate the safety, tolerability, pharmacokinetic characteristics and effectiveness of hec169096 in patients with thyroid cancer, non-small cell lung cancer, and other advanced solid tumors.

this is an open-label, multi-center phase 1/2 study in participants with advanced solid tumors, including ret fusion-positive nsclc, mtc, and other tumors with ret activation. phase i of this study includes a dose-escalation phase and a dose-expansion phase , which will focus on exploring mtd and/or rp2d of hec169096 in patients with advanced solid tumours; phase ii will assess the efficacy and safety of hec169096 at the rp2d dose.

Eligibility criteria:
inclusion criteria: * phase 1：pathologically documented, definitively diagnosed non-resectable advanced solid tumor. * phase 2： all participants must have an oncogenic ret-rearrangement/fusion or mutation (excluding synonymous, frameshift, and nonsense mutations) solid tumor. * participants has eastern cooperative oncology group (ecog) performance status (ps) of 0-2. * measurable or non-measurable disease as determined by recist 1.1; * adequate hematologic, hepatic and renal function; * life expectancy of at least 12 weeks; * negative pregnancy test (urine or serum) for female patients of childbearing potential; * participants agrees to provide tumor tissue (archived, if available or a fresh biopsy). exclusion criteria: * participant's cancer has a known primary driver alteration other than ret. * nitrosourea, anthracyclines and mitomycin chemotherapy within 6 weeks prior to study treatment; * chemotherapy, immunotherapy, radiotherapy, or major surgery within 4 weeks or 5 half-lives (whichever is longer) prior to study treatment; * those who have received more than 30% of bone marrow radiation or wide-range radiotherapy within 4 weeks before the first study drug treatment (the patients receiving palliative radiotherapy are within 2 weeks before receiving study drug treatment); * had received traditional chinese medicine for anti-tumor within a week before receiving study drug treatment; * had received live vaccine within 4 weeks prior to study treatment; * had received any investigational agent from other clinical study within 4 weeks or 5 half-lives (whichever is longer) prior to study treatment or are currently participating in other clinical trials; * any unresolved toxicities from prior therapy greater than common terminology criteria for adverse events (ctcae) grade 1 at the time of starting study treatment . * central nervous system (cns) metastases or a primary cns tumor that is associated with progressive neurological symptoms. * patients with other malignant tumors within 5 years before the first use of drugs * patients have a history of severe cardiovascular disease; * active hepatitis (hepatitis b: hbsag-positive and hbv-dna ≥ 2000 iu/ ml or ≥ 10\^4 cps/ ml; hepatitis b: hcv antibody-positive and hcv-rna positive), hiv antibody-positive. * patients with clinically active interstitial lung disease, active pneumonia, and radiation pneumonia requiring treatment; * poorly controlled pleural effusion, abdominal effusion, or pericardial effusion after intervention (such as drainage); * clinically significant active malabsorption syndrome or other diseases that may affect study drug administration and gastrointestinal absorption; * patients have been treated with any strong cyp3a inhibitors or inducers within 2 weeks prior to the first dose or ppis in the first week before the first dose.