Phase1/2a Study for IPG7236 in Patients With Advanced Solid Tumors

Inclusion Criteria:

1. A written informed consent must be signed prior to performing any study procedures.

2. Male or females 18 years or older.

3. Diagnosis of advanced or recurrent, histologically or cytologically confirmed, asolid malignancy that is either metastatic or unresectable.

• Part 1 Dose Escalation: all solid tumor types.

• Part 2 Dose Expansion: the following tumor types are tentatively planned forexpansion. It may be modified based on the results from the dose escalationphase.

• Renal cancer

• Triple-negative breast cancer

• Head and neck cancer

• Melanoma

4. Subjects must have failed established standard medical anti-cancer therapies for agiven tumor type or have been intolerant to such therapy, or in the opinion of theInvestigator have been considered ineligible for standard therapies on medicalgrounds.

5. Subjects must demonstrate measurable disease, per Response Evaluation Criteria inSolid Tumors (RECIST) v1.1.

6. Subjects must have a life expectancy of ≥ 3 months.

7. Subjects must have an Eastern Cooperative Oncology Group(ECOG) performance statusscore of 0 to 1.

8. Subjects must have adequate hematologic and organ function as indicated by thefollowing laboratory values

9. Hematologic

• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L.
• Platelet count ≥ 100×109/L
• Hemoglobin ≥ 9 g/dL (subjects that required transfusion or growth factorneed to demonstrate stable hemoglobin for 7 days of 9 g/dL)

2. Renal • Estimated glomerular filtration rate（eGFR ）≥ 50 mL/min OR serum creatinine ≤ 1.5 × upper limit of normal (ULN).

3. Hepatic

• Aspartate aminotransferase levels ≤ 3 ×ULN (if liver metastases arepresent, ≤ 5× ULN)
• Alanine aminotransferase levels ≤ 2.5 × ULN (if liver metastases arepresent, ≤ 5×ULN).
• Bilirubin ≤ 1.5 × ULN

4. Coagulation • Prothrombin time and activated partial thromboplastin time ≤ 1.5 × ULN

5. Subjects must be able to swallow and retain orally administered medication.

6. Patients must be willing and able to comply with all scheduled visits, treatment,laboratory tests, be able to take oral medication, and other requirements of thestudy

7. Female patients of child-bearing potential must have a negative pregnancy test.

8. Female patient who is of child-bearing potential is eligible to participate but mustuse an acceptable form of birth control method, including abstinence, hormonalcontraception for at least 3 months in combination with a barrier method,intrauterine device (placement at least 3 months prior to screening), diaphragm withspermicide, cervical cap, condoms with contraceptive gel/foam /cream, or surgicalsterilization (tubal ligation at least 6 months prior to screening) or partner whohad a vasectomy at least 6 months prior to screening

9. Male patient with a female partner of child-bearing potential is eligible toparticipate but must be either documented to be surgically sterile (vasectomy),practicing complete abstinence for 90 days after study drug administration, or usingtwo adequate forms of highly effective contraception (together with the femalepartner), one of which should be a physical barrier method, for 90 days after thestudy drug administration.

Exclusion Criteria:

1. Subjects with primary malignancy of the central nervous system or malignanciesrelated to human immunodeficiency virus (HIV) or solid organ transplant.

2. Subjects who have not recovered from all toxic effects from prior antitumor therapyor surgical procedures, defined as toxicities (other than alopecia) not yet resolvedto Grade ≤ 1 according to NCI CTCAE v5.0.

3. Subjects with recent prior therapy defined as

4. Any investigational or Food and Drug Administration (FDA)-approved anti-cancerdrug within 14 days or 5 half-lives, whichever is longer, prior to the firstdose of study drug.

5. Any radiotherapy, chemotherapy, targeted therapy or immunotherapy within 14days or major surgery within 28 days or anti-neoplastic antibody ornitrosoureas/mitomycin C within 42 days prior to the first dose of study drug

6. Subjects with any uncontrollable diseases (e.g., severe mental, neurological,cardiovascular, respiratory, and other systemic diseases) or obvious activeinfections that may affect the clinical study.

7. Subjects with positive Coronavirus disease（COVID）-19 PCR tests (patients whorecovered from COVID-19 but have positive COVID-19 PCR tests may be included at thejudgment of the Investigator)

8. Subjects who have received the live or attenuated vaccine within 4 weeks prior tostudy treatment or intend to receive a live or attenuated vaccine during the study

9. Presence of hepatitis B surface antigen (HBsAg) or positive hepatitis C antibodytest result at screening or within 3 months prior to the first dose of studytreatment. History of known HIV infection. Note:

10. Subjects with positive Hepatitis C antibody due to prior resolved disease canbe enrolled only if a confirmatory negative Hepatitis C RNA polymerase chainreaction (PCR) is obtained.

11. Subjects with well-controlled HIV may be enrolled if all the following criteriaare met:

• must be stable on their anti-retroviral regimen, and participants must behealthy from an HIV perspective
• Participants must have a cluster of differentiation 4（CD4） count ofgreater than 250 cells/micro litre（mcL ）over the past 6 months on thissame anti-retroviral regimen and must not have had a CD4 count < 200cells/mcL over the past 2 years unless it was deemed related to THE CANCERAND/OR CHEMOTHERAPY-induced bone marrow suppression
• For patients who have received chemotherapy in the past 6 months, aCD4 count < 250 cells/mcL during chemotherapy is permitted as long asviral loads were undetectable during this same chemotherapy
• Participants must have an undetectable viral load and a CD4 count >= 250cells/mcL within 7 days of enrollment
• Participants must not be currently receiving prophylactic therapy for anopportunistic infection and must not have had an opportunistic infectionwithin the past 6 months. HIV-infected patients should be monitored every 12 weeks for viral load and CD4 counts

8. Previous malignant disease (other than the target malignancy to be investigated inthis trial) within the last 3 years. Subjects with a history of cervical carcinomain situ, superficial or non-invasive bladder cancer or basal cell or squamous cellcancer in situ previously treated with curative intent may be included at thejudgment of the Investigator.

9. Subjects with symptomatic or untreated leptomeningeal or brain metastases or spinalcord compression. Note: Subjects previously treated for these conditions that havehad stable central nervous system (CNS) disease (verified with consecutive imagingstudies) for >1 month, are asymptomatic and off corticosteroids, or are on a stabledose of corticosteroids for at least 1 month prior to study Day 1 are permitted. Thestability of brain metastases must be confirmed with imaging. The subject treatedwith gamma knife therapy can be enrolled 2 weeks post-procedure as long as there areno post procedure complications or the subject is stable.

10. Subjects with active upper digestive tract ulcer or other disorders that can affectdrug absorption, distribution, metabolism or clearance.

11. Subjects with a marked baseline prolongation of QT/corrected QT interval（QTc）interval (e.g., repeated demonstration of a QTc interval >480 milliseconds (CTCAEgrade 1) using Fridericia QT correction formula.

12. Subjects using concomitant medications known to prolong the QT/QTc interval.

13. Pregnancy or breastfeeding female; Female patients must be surgically sterile or bepostmenopausal, or must agree to the use of effective contraception during theperiod of therapy. All female patients with reproductive potential must have anegative pregnancy test (serum or urine) prior to enrollment. Male patients must besurgically sterile or must agree to use effective contraception during the period oftherapy. The definition of effective contraception will be based on the judgment ofthe principal investigator or a designated associate.

14. Subjects who are unable to comply with study and follow-up procedures