colorectal cancer
Conditions
Interventions
A:HRS-4642 combined with SHR-9839
B:HRS-4642 combined with SHR-9839 and FOLFIRI
C:HRS-4642 combined with SHR-9839 and FOLFOX
D:HRS-4642 combined with SHR-9839 (RP2D-A)
E:HRS-4642 combined with SHR-9839 and FOLFIRI (RP2D-B)
F:HRS-4642 combined with SHR-9839 and FOLFOX (RP2D-C)
Sponsors
Fudan University Shanghai Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. metastatic colorectal adenocarcinoma diagnosed by pathological histologic examination; 2. age 18-75 years old; 3. expected survival >= 12 weeks; 4. an ECOG score of 0-1; 5. at least one measurable lesion according to RECIST version 1.1 criteria; 6. normal major organ and bone marrow function prior to first use of study drug; 7. patients volunteered to participate and signed an informed consent form.
Exclusion criteria
Exclusion criteria: 1. Concomitant active malignancy other than the primary tumor (in addition to cured basal cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, intraductal carcinoma of the breast in situ, papillary thyroid carcinoma, and gastrointestinal tract tumors confirmed to have been cured by endoscopic mucosal resection); history of a prior malignancy (patients with disease that has been cured for =2 years are eligible for enrollment); 2. Patients with untreated or active central nervous system (CNS) tumor metastases or meningeal metastases; patients may be enrolled in the study if they have already received local therapy and the patient's neurological symptoms are able to stabilize for at least 2 weeks prior to the first dose and do not require hormonal therapy or are receiving =10 mg/day of prednisone (or hormonal equivalent); 3. The presence of serious complications (perforation, obstruction, hemorrhage that cannot be managed by internal medicine, etc.) in the primary lesion 4. Receipt of the following treatments or medications prior to the first study treatment: a) major surgery within 28 days prior to the first study drug treatment (tissue biopsy for diagnostic reasons is permitted) b) Received systemic antitumor therapy 4 weeks prior to initiation of study treatment or no more than 5 half-lives from the last antitumor dose; c) Completion of palliative radiotherapy or localized treatment of target lesion rows within 14 days prior to the first dose, except for localized treatments such as for pain relief; d) Herbal medicines with anti-tumor indications within 2 weeks prior to the first administration of the study drug; and e) Other unlisted clinical investigational drugs or treatments within 28 days prior to the first dose of study drug; f) Use of potent/moderately potent drugs that inhibit or induce the hepatic drug metabolizing enzymes CYP3A4/5 or CYP2C8 in the 14 days prior to the first dose of study drug); Drugs that may have an effect on P-gp and glucuronosyltransferase (UGT) will be required during the study; g) Use of live attenuated vaccines within 4 weeks prior to the first dose or anticipated need for live attenuated vaccines during the study; 5. Toxicity and/or complications from prior interventions that have not recovered to NCI-CTCAE = Grade 1 or to the level specified by the entry criteria (except for toxicities judged by the investigator to be safe and manageable, e.g., alopecia areata, peripheral neuropathy = Grade 2, etc.); 6. Subjects with a history of interstitial pneumonitis or imaging at screening suggestive of suspected interstitial pneumonitis or inability to exclude interstitial pneumonitis; or other moderate-to-severe lung disease that severely affects lung function; or those who have received >30 Gy of chest radiation therapy within 24 weeks prior to the first dose; 7. Subjects with active tuberculosis or a history of active tuberculosis infection within =48 weeks prior to screening, with or without treatment; 8. Moderate or severe ascites with clinical symptoms; uncontrolled or moderate or greater amounts of pleural effusion and pericardial effusion 9. Have severe cardiovascular disease, including but not limited to: a) Left ventricular ejection fraction (LVEF) <50% within 28 days prior to first dose; b) Have severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias, degree II-III atrioventricular block requiring clinical intervention; c) Acute coronary syndrom
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate;Recommended Phase 2 Dose;Dose-Limiting Toxicity; | — |
Secondary
| Measure | Time frame |
|---|---|
| progression free survival;disease control rate;duration of remission;overall survival;Adverse events; | — |
Countries
China
Contacts
Public ContactSanjun Cai; Zhiyu Chen
Fudan University Shanghai Cancer Center
Outcome results
None listed