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

Inclusion Criteria:

1. The patient must voluntarily participate in this clinical study and be willing andable to provide written informed consent/assent for the trial.

2. Age ≥ 18 years old on the day of signing informed consent form (ICF), males orfemales

3. Patient population:

4. In Part I: The patient must have histologically or cytologically confirmedadvanced solid tumor that is refractory to standard treatment or for which nostandard treatment exists, including but not limited to triple-negative breastcancer (TNBC), SCLC, ovarian cancer (OC) and metastatic castration-resistantprostate cancer (mCRPC).

5. In Part II: The patients must be histologically or cytologically confirmedES-SCLC with disease progression after one and only one course of 1L standardplatinum-based therapy. Anti-PD-1 or anti-PD-L1 antibody therapy is acceptableas long as it's part of the 1L treatment. Including platinum sensitive andplatinum resistant patients. Platinum sensitive is defined as the relapse-freeinterval exceeds 90 days after treatment with platinum doublets is completed;The platinum resistant represents disease relapses within 90 days of treatmentcompletion during a chemotherapy-free interval (CFI).

6. In Part I: Patients have an ECOG performance status of 0 to 1.

7. In Part II: Patients have an ECOG performance status of 0 to 2.

8. Patients have a life expectancy of ≥12 weeks.

9. In Part II: patients have at least 1 measurable lesion per RECIST v1.1,including a previously irradiated lesion if has progressed since radiotherapy,that can be accurately measured at baseline which is suitable for accuraterepeated measurements

10. Patients have adequate organ function, as indicated by the following laboratoryvalues (had not received blood transfusion, apheresis infusion, erythropoietin,granulocyte colony-stimulating factor, and other relevant medical support within 28days before the administration of the IPs

11. Female patients should meet at least 1 of the following criteria before they canparticipate in the study:

• Females who have no childbearing potential (i.e., physiologically incapable ofpregnancy), including those who have undergone hysterectomy, bilateraloophorectomy, or bilateral salpingectomy.

• Post-menopausal (total cessation of menses for ≥1 year).

• For those with childbearing potential, they should have a negative serumpregnancy test during the screening period (within 7 days prior to the firstdose of the IPs), should not be in lactation, and willing to take effectivecontraceptive measures throughout the study period, from study entry up to 6months after the last dose of the IP(s).

6. Male patients are eligible to participate in the study if they have undergonevasectomy or agree to use effective methods of contraception from study entry up to 6 months after the last dose of the IP(s).

Exclusion Criteria:

1. Patients with primary tumor in central nervous system (CNS) and active or untreatedcentral CNS metastases and/or carcinomatous meningitis should be excluded. Patientswith previously treated brain metastases may participate provided they areclinically stable for at least 4 weeks and, have no evidence of new or enlargingbrain metastases and no requirements for corticosteroids 14 days prior to dosingwith IPs.

2. Patients with serious acute and chronic infections, including:

• Patients with an uncontrolled acute infection, or an active infection requiringsystemic treatment, or patients who have received systemic antibiotics within 2weeks prior to the first dose of the IPs; prophylaxis use of systemicantibiotics treatment for upper tract infection is allowed as long as noviolation 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 testingshould undergo CD4+ T-cell test during the screening period. Patients with CD4+T-cell counts < 350 cells/uL are ineligible for enrollment. Patients withunknown HIV infection status who are unwilling to undergo HIV testing shouldnot 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 testedfor hepatitis B virus (HBV) DNA titer (excluding patients with a DNA titer ofmore than 2500 copies [cps]/mL or 500 IU/mL) and HCV RNA (excluding patientswith 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 afterdrug treatment (DNA titer not exceeding 2500 copies [cps]/mL or 500 IU/mL) andhepatitis C infected patients who received treatment and achieved sustainedvirologic response for at least 12 weeks can be enrolled.

• Note: If the lower detection limit of the HBV DNA assay in the study centers ishigher than 2500 copies [cps]/mL or 500 IU/mL, the patients in the study centerwith an HBV DNA assay result lower than the lower detection limit of the assaycan 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 firstdose of the IPs (the patient can be enrolled if the elution period prior to thefirst dose of the IPs is ≥5 half-lives), or patients who need to continue receivingthese medications during the study period.

5. Patients who have received a live-virus vaccination within 28 days of the plannedstart of study.

6. Patients who have participated a study of an investigational agent and receivedstudy therapy or used an investigational device within 28 days of the first dose oftreatment.

7. Patients have not recovered (i.e., to ≤Grade 1 or to baseline, as evaluated byNCI-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 orproprietary Chinese medicine), or other anti-cancer systemic treatment (exceptanti-cancer antibody) within 5 half-lives or 14 days, whichever is longer prior tothe first dose of the IPs. Patients who have received anti-cancer antibody within 28days prior to the first dose of the IPs.

9. Patients who have undergone a major surgery within 28 days prior to the studytreatment, or have undergone a radical radiotherapy, or have undergone a palliativeradiotherapy within 14 days prior to the study treatment, or have used a radioactivedrug (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 priorto the first dose of the IPs will be excluded. except for radically treated locallycurable malignant tumors, such as basal or squamous cell skin cancer, superficialbladder cancer, or prostate, cervical or breast carcinoma in situ.

11. Patients with uncontrolled pleural effusion, pericardial effusion or ascitesrequiring recurrent drainage procedures (once monthly or more frequently). Pleasecontact 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 acutemyocardial infarction, unstable angina, stroke, or transient ischemic attack within 6 months prior to the first dose of the IPs; patients who have congestive heartfailure (≥New York Heart Association [NYHA] Classification Class II); patients whohave 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 gastrointestinalillnesses that may affect the absorption of oral medication IMP4297 andtemozolomide.

16. Patients with a known hypersensitivity to IMP4297, temozolomide or any of theexcipients of the products.

17. Patients who have received transplantation including patients with previousallogeneic 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 patientat risk in IP administration or may affect the evaluation of toxicity events or AEs.