IMP4297 in Combination With Temozolomide in Patients With Advanced Solid Tumors and Small Cell Lung Cancer

Exclusion Criteria

• •1. Patients with primary tumor in central nervous system (CNS) and active or untreated central CNS metastases and/or carcinomatous meningitis should be excluded. Patients with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks and, have no evidence of new or enlarging brain metastases and no requirements for corticosteroids 14 days prior to dosing with IPs.
• •2. Patients with serious acute and chronic infections, including:
• •* Patients with an uncontrolled acute infection, or an active infection requiring systemic treatment, or patients who have received systemic antibiotics within 2 weeks prior to the first dose of the IPs; prophylaxis use of systemic antibiotics treatment for upper tract infection is allowed as long as no violation with the requirement in Section 6.5 Concomitant Therapy.
• •* Patients who have a known history of human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome or positive HIV testing should undergo CD4+ T-cell test during the screening period. Patients with CD4+ T-cell counts \< 350 cells/uL are ineligible for enrollment. Patients with unknown HIV infection status who are unwilling to undergo HIV testing should not be enrolled in the study;
• •* Patients who have known active hepatitis B or C. To be included in the study, patients with hepatitis B virus surface antigen (HBsAg) or hepatitis C virus (HCV) antibody positive test results during screening must be further tested for hepatitis B virus (HBV) DNA titer (excluding patients with a DNA titer of more than 2500 copies \[cps\]/mL or 500 IU/mL) and HCV RNA (excluding patients with an HCV RNA concentration exceeding the lower detection limit of the assay) to exclude active hepatitis B or hepatitis C infection requiring treatment. Hepatitis B virus carriers, patients with stable hepatitis B infection after drug treatment (DNA titer not exceeding 2500 copies \[cps\]/mL or 500 IU/mL) and hepatitis C infected patients who received treatment and achieved sustained virologic response for at least 12 weeks can be enrolled.
• •* Note: If the lower detection limit of the HBV DNA assay in the study centers is higher than 2500 copies \[cps\]/mL or 500 IU/mL, the patients in the study center with an HBV DNA assay result lower than the lower detection limit of the assay can be enrolled.
• •* Active tuberculosis
• •3. Patients who have previously received PARP inhibitors.
• •4. Patients who have received strong CYP3A4 inhibitors or inducers prior to the first dose of the IPs (the patient can be enrolled if the elution period prior to the first dose of the IPs is ≥5 half-lives), or patients who need to continue receiving these medications during the study period.
• •5. Patients who have received a live-virus vaccination within 28 days of the planned start of study.
• •6. Patients who have participated a study of an investigational agent and received study therapy or used an investigational device within 28 days of the first dose of treatment.
• •7. Patients have not recovered (i.e., to ≤Grade 1 or to baseline, as evaluated by NCI-CTCAE v5.0) from cytotoxic therapy-induced AEs, except for alopecia.
• •8. Patients who have received anti-cancer chemotherapy, endocrine therapy, herbal/alternative therapies (including Chinese herbal or Chinese medicine or proprietary Chinese medicine), or other anti-cancer systemic treatment (except anti-cancer antibody) within 5 half-lives or 14 days, whichever is longer prior to the first dose of the IPs. Patients who have received anti-cancer antibody within 28 days prior to the first dose of the IPs.
• •9. Patients who have undergone a major surgery within 28 days prior to the study treatment, or have undergone a radical radiotherapy, or have undergone a palliative radiotherapy within 14 days prior to the study treatment, or have used a radioactive drug (Strontium, Samarium, etc.) within 56 days prior to the study treatment.
• •10. In Part II of the study, patients who have other malignancies within 2 years prior to the first dose of the IPs will be excluded. except for radically treated locally curable malignant tumors, such as basal or squamous cell skin cancer, superficial bladder cancer, or prostate, cervical or breast carcinoma in situ.
• •11. Patients with uncontrolled pleural effusion, pericardial effusion or ascites requiring recurrent drainage procedures (once monthly or more frequently). Please contact medical monitor if any further discussion or clarification is needed.
• •12. Patients with a history of seizures.
• •13. Patients with a previously documented diagnosis of myelodysplastic syndrome (MDS).
• •14. Patients who have major cardiovascular diseases (such as congestive heart failure, unstable angina, atrial fibrillation, arrhythmia); patients who have acute myocardial infarction, unstable angina, stroke, or transient ischemic attack within 6 months prior to the first dose of the IPs; patients who have congestive heart failure (≥New York Heart Association \[NYHA\] Classification Class II); patients who have severe arrhythmia requiring medication (including QT interval \[QTc\] prolongation corrected by the Fridericia's formula \[QTcF\] of more than 480 msec, pacemaker installation, and previous diagnosis of congenital long QT syndrome).
• •15. Patients who are unable to swallow capsules. Patients have gastrointestinal illnesses that may affect the absorption of oral medication IMP4297 and temozolomide.
• •16. Patients with a known hypersensitivity to IMP4297, temozolomide or any of the excipients of the products.
• •17. Patients who have received transplantation including patients with previous allogeneic bone marrow transplant.
• •18. Patients known to have a history of alcoholism or drug abuse.
• •19. The investigator believes that the patient's underlying disease may put the patient at risk in IP administration or may affect the evaluation of toxicity events or AEs.