Afuresertib +Sintilimab+Chemotherapy in Patients With Selected Solid Tumors That Resistance to Prior Anti-PD-1/PD-L1

Inclusion Criteria: 1. Be \>=18 years of age on the day of signing the informed consent and be able to provide written informed consent for the trial. 2. Prior treatments: * In phase I, patients had at least 1 prior systemic anti-cancer treatment (including neoadjuvant/adjuvant therapy are qualified to be enrolled). Patients who resistant to anti-PD-1/PD-L1 are preferred. * In phase II, patients should meet the following 2 criteria simultaneously: A: resistant to anti-PD-1/PD-L1: previously received at least 6 weeks （2 cycles） anti-PD-1/PD-L1 (including neoadjuvant/adjuvant therapy) and progressed after anti-PD-1/PD-L1 or their combination therapies. B: received \<=3 lines systematic therapy during recurrent/metastatic period. 3. Tumor diagnosis: * In phase I, patients had a histology confirmed diagnosis of locally advanced or metastatic solid tumors who had at least 1 prior systemic anti-cancer treatment including neoadjuvant/adjuvant therapy are qualified to be enrolled. The patients with the 5 selected cancer types below who resistant to prior anti-PD-1/PL-1 or its combination therapies will be enrolled with a higher priority. * In phase II, the patients have only the following diagnoses will be allowed: * CC: Patients with histologically confirmed metastatic, recurrent or persistent squamous cell carcinoma, adenosquamous carcinoma, adenocarcinoma of the cervix are allowed. The other histological types of cervical cancer will be excluded. * EC: Patients with histologically confirmed metastatic, recurrent or persistent Epithelial Endometrial Carcinoma with endometrioid, high grade serous, or clear cell carcinoma. The other histological types of endometrial cancer will be excluded. * EsC: Patients with histologically confirmed local advanced, recurrent or metastasis esophageal squamous cell carcinoma or Her2- adenocarcinoma. * NSCLC: Patients with histologically confirmed locally advanced, recurrent, or metastatic Non-Small Cell Lung Cancer (squamous cell carcinoma or adenocarcinoma, adenosquamous carcinoma), who have EGFR wild type status, KRAS wild type status and ALK- negative rearrangement status. * GC/GEJC: Patients with histologically confirmed locally advanced, recurrent, or metastatic Her2- gastric adenocarcinoma or gastroesophageal junction adenocarcinoma or squamous cell carcinoma allowed. 4. Biomarker test: * In phase I, the biomarker test with tumor sample is optional. However, blood test of cfDNA is required. * In phase II, if patient has prior tumor sample PTEN/PI3K/AKT gene alterations or immunohistochemistry test with a report, no further tumor sample biomarker test is needed, but the blood cfDNA test is still required in this study. Otherwise, patient should be able to provide archival or biopsy tumor samples for PTEN immunohistochemistry and PTEN/PI3K/AKT gene alterations, and/or the blood sample for PTEN/PI3K/AKT gene alterations for the cell-free DNA (cfDNA) test. The archival tumor tissue sample obtained better within 2 year from study enrollment or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated will be accepted for IHC test and gene sequencing test. Formalin-fixed, paraffin embedded tissue blocks are preferred to be sectioned on the slides. * Please contact sponsor if patient cannot provide archival or biopsy tumor samples. 5. Patients who are suitable for nab-paclitaxel or docetaxel judged by investigator. 6. Have measurable disease per RECIST 1.1 as assessed by local radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. 7. Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2. 8. Have adequate organ function as defined below. Specimens must be collected within 10 days prior to the start of study treatment. 1. Hematological: Absolute neutrophil count (ANC) ≥ 1.5 × 109 /L Platelet count ≥100 × 109 /L Hemoglobin ≥ 90 g/L * Criteria must be met without granulocyte-colony stimulating factor, erythropoietin dependency and without packed red blood cell transfusion within last 2 weeks. 2. Renal Creatinine ≤1.5 × upper limit of normal (ULN) OR Measured or calculated per institutional standard creatinine clearance (glomerular filtration rate can also be used in place of creatinine or creatinine clearance) ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN. 3. Hepatic Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN. AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases). 4. Coagulation International normalized ratio (INR) OR prothrombin time (PT) and Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy, as long as PT or aPTT is within therapeutic range of intended use of anticoagulants. 9. Fasting glucose ≤126 mg/dL or ≤7.0 mmol/L for patients without type 2 diabetes and ≤167 mg/dL or ≤9.3 mmol/L for patients with type 2 diabetes; OR glycosylated hemoglobin (HbA1c) ≤8%. 10. Life expectancy of 12 weeks or more based on investigator's assessment. 11. Patients have recovered from adverse events associated with chemotherapy, radiation and surgical operation as pre-treatment to Grade 1 or lower with CTCAE v5.0 excluding stable symptoms (e.g. alopecia, skin hyperpigmentation.). 12. Patients must agree to use effective contraception during the study and for at least 16 weeks after discontinuation as following: 1. Total abstinence (if it is their preferred and usual lifestyle) 2. An intrauterine device or hormone-releasing system 3. A contraceptive implant 4. An oral contraceptive (with additional barrier method) OR 5. Have a vasectomized partner with confirmed azoospermia. 6. Male patients must agree to use an adequate method of contraception. 13. Patient is able to swallow and retain oral medication without gastrointestinal diseases to interfere with drug absorption. Exclusion Criteria: 1. Pregnancy or lactation. A woman of child-bearing potential, who has a positive urine pregnancy test prior to treatment. If the urine test is cannot be confirmed as negative, a serum pregnancy test will be required. 2. Prior anti-cancer treatment or any investigational agent within 28 days (or 5 half-lives, whichever is shorter) prior to the first dose of study drugs. 3. Patients that have previously received AKT or PI3 kinase pathway or mTOR inhibitors will not be enrolled. 4. Patients that discontinued prior anti PD-1/PD-L1 due to immune related AE. 5. Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. 6. With clinically uncontrolled pleural effusion/ascites (patients who do not need effusion drainage or have no significant increase in effusion 3 days after stopping drainage can be enrolled); 7. With a tumor compressing the surrounding important organs, compressing the superior vena cava, or invading the mediastinal great vessels, heart, etc.; 8. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. 9. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug. 10. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, transitional cell carcinoma of urothelial cancer, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. 11. History of seizure of condition that may predispose to seizure that needs anti-epileptic medications; brain arteriovenous malformation; or intracranial masses, such as schwannomas and meningiomas that are causing edema or mass effect. 12. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment. 13. Has severe hypersensitivity (≥Grade 3) to Sintilimab or afuresertib and/or any of their excipients. 14. Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs) prior to the first dose of study treatment. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. 15. Has a history of (non-infectious) pneumonitis that required steroids or has concurrent interstitial pneumonia. 16. Has an active infection requiring systemic therapy, active syphilis infection, active pulmonary tuberculosis infection，HIV-infection (i.e., HIV 1 or 2 antibody positive). 17. New York Heart Association congestive heart failure of grade II or above, unstable angina, myocardial infarction within the past 6 months or serious cardiac arrhythmia associated with significant cardiovascular impairment within the past 6 months. 18. Prolongation of corrected QTc interval, as corrected by the Fridericia's correction formula to greater than 450 mSec for males and 470 mSec for females: unless prolonged QTc interval due to right bundle branch block or left bundle branch block with a pacemaker. 19. Presence of uncontrolled hypertension (systolic blood pressure (BP) \>160 mmHg or diastolic BP\>100 mmHg). Patients with a history of hypertension are allowed, provided that BP is controlled to within these limits by anti-hypertensive treatment. 20. Has known untreated active Hepatitis B (defined as HBsAg (+) and HBV DNA ≥200 IU/mL (1000 copies/ml)) or active Hepatitis C virus infection (defined as HCV antibody positive and HCV-RNA level above the lower limit of detection). Note: Subjects with HBV DNA \< 200 IU/ml or below the lower limit of detection are eligible. Those on active HBV therapy with viral loads under 200 IU/mL should stay on the same therapy throughout study treatment. 21. Has a known psychiatric or substance abuse disorder that would interfere with the patient's ability to cooperate with the requirements of the study. 22. Patients receiving a strong CYP3CA, OATP, BRCP substrate or inducer are not eligible. Please see protocol related section for the list of prohibited medications. 23. Has had an allogenic tissue/solid organ transplant. 24. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating investigator. 25. Patient needs radiotherapy during this study.