A Study of AK104 in Combination With Chiauranib in Patients With Extensive Stage Small Cell Lung Cancer

Small cell lung cancer (SCLC) consists 15% of the lung cancer.Because of the high malignancy, poor cell differentiation, and rapid proliferation of SCLC, 65% of the patients were in the extensive stage at their first presentation in the hospital with a very poor prognosis. There were few options of second-line therapies for patients who experienced progress disease during or after the end of first-line platinum-based regimens. Several studies showed that PD-1/PD-L1 inhibitors had synergistic anti-tumor effects with anti-vascular endothelial growth factor(VEGF) agents, i.e., PD-1/PD-L1 inhibitors could restore the anti-tumor effect of the immune system by blocking PD-L1, and anti-VEGF agents could improve the efficacy of the former by blocking the immunosuppressive effect of VEGF and promoting the infiltration of T cells in tumor tissues. Immunotherapy in combination with antiangiogenic therapy may become a trend in the treatment of extensive stage small cell lung cancer(ES-SCLC). The aim of this international multicentre phase Ib/II trial is to evaluate the efficacy-objective response rate according to RECIST criteria and safety-incidence and severity of adverse events.The patients' recruitment timeframe is set at 16 months and approximately 42 patients will be included.

Inclusion criteria

• The subject must sign the written informed consent form (ICF) voluntarily.
• Aged ≥ 18 to ≤ 75 years.
• Eastern Cooperative Oncology Group(ECOG) performance status score of 0 or 1.
• Life expectancy≥ 3 months.
• Histologically or cytologically confirmed ES-SCLC according to the Veterans Administration Lung Study Group(VALG) stage.
• Phase Ib and II: Subjects with ES-SCLC who have failed prior first-line platinum-based chemotherapy in combination with PD1/PDL1 inhibitors will be enrolled.
• At least 1 measurable lesion per RECIST v1.1, which is applicable for repeated accurate measurement. Brain metastatic lesions are not considered target lesions.
• Adequate organ function.
• Women of childbearing potential must have a negative urine or serum pregnancy test
• If a nonsterile male subject has sexual intercourse with a female partner of childbearing potential, he must use an effective method of contraception from the start of screening until Day 120 after the last dose; it should be discussed with the Investigator whether contraception should be discontinued after this time point.
• Subjects must be willing and able to comply with the scheduled visits, treatment regimens, laboratory tests, and other requirements in the study.

Exclusion criteria

• Malignancies other than SCLC within 3 years prior to enrollment. However, subjects with other malignancies that have been cured are eligible.
• Concurrent enrollment in another clinical study, unless it is an observational, non-interventional clinical study or a follow-up period of an interventional study.
• Subjects whose imaging at screening shows that the tumor encircles important blood vessels or has significant necrosis and cavitation, and the subjects'participation is associated with a risk of hemorrhage.
• Tumor invasion of surrounding vital organs and blood vessels.
• Subjects who had active autoimmune disease that required systemic treatment in the past two years.
• Subjects with prior history of non-infectious pneumonitis/interstitial lung disease requiring systemic glucocorticoid therapy or with non-infectious pneumonitis at present.
• Presence of metastases to brainstem, meninges and spinal cord, or spinal cord compression.
• Subjects with pleural effusion, pericardial effusion, or ascites that are clinically symptomatic or require drainage.
• Subjects with unresolved toxicity due to prior anti-tumor therapy, defined as failure to recover to National Cancer Institute Common Terminology Criteria for Adverse Events(NCI CTCAE) v5.0 Grade 0 or 1 (except for alopecia) or to the levels specified in the inclusion/exclusion criteria.
• Subjects who cannot swallow pills, and who have malabsorption syndrome, or any condition affecting gastrointestinal absorption. Subjects with active or prior history of definite inflammatory bowel disease.
• Subjects with a history of immunodeficiency; a positive human immunodeficiency virus (HIV) antibody test; and current long-term use of systemic corticosteroids or other immunosuppressants.
• Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
• Subjects who had major surgical procedure or serious trauma within 30 days prior to the first dose, or a major scheduled surgery within 30 days after the first dose; subjects who had minor local surgery within 3 days prior to the first dose.