SCLC,Extensive Stage
Conditions
Brief summary
A Phase Ib/II open label,international multicentre study to evaluate the efficacy and safety of anti-PD-1 and CTLA-4 bispecific antibody AK104 in combination with Chiauranib in Patients with Extensive Stage Small Cell Lung Cancer Who Failed First-line Platinum-based Chemotherapy in Combination with PD1/PDL1 Inhibitors
Detailed description
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.
Interventions
DRUGAK104 IV infusion；Chiauranib oral
AK104 IV infusion once every 3 weeks；Chiauranib once a day oral
Sponsors
Chipscreen Biosciences, Ltd.
Akeso
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. The subject must sign the written informed consent form (ICF) voluntarily. 2. Aged ≥ 18 to ≤ 75 years. 3. Eastern Cooperative Oncology Group(ECOG) performance status score of 0 or 1. 4. Life expectancy≥ 3 months. 5. Histologically or cytologically confirmed ES-SCLC according to the Veterans Administration Lung Study Group(VALG) stage. 6. 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. 7. At least 1 measurable lesion per RECIST v1.1, which is applicable for repeated accurate measurement. Brain metastatic lesions are not considered target lesions. 8. Adequate organ function. 9. Women of childbearing potential must have a negative urine or serum pregnancy test 10. 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. 11. Subjects must be willing and able to comply with the scheduled visits, treatment regimens, laboratory tests, and other requirements in the study.
Exclusion criteria
1. Malignancies other than SCLC within 3 years prior to enrollment. However, subjects with other malignancies that have been cured are eligible. 2. Concurrent enrollment in another clinical study, unless it is an observational, non-interventional clinical study or a follow-up period of an interventional study. 3. 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. 4. Tumor invasion of surrounding vital organs and blood vessels. 5. Subjects who had active autoimmune disease that required systemic treatment in the past two years. 6. Subjects with prior history of non-infectious pneumonitis/interstitial lung disease requiring systemic glucocorticoid therapy or with non-infectious pneumonitis at present. 7. Presence of metastases to brainstem, meninges and spinal cord, or spinal cord compression. 8. Subjects with pleural effusion, pericardial effusion, or ascites that are clinically symptomatic or require drainage. 9. 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Up to approximately 2 years | ORR is proportion of subjects with complete response(CR) or partial response(PR), based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1 |
| Incidence and severity of adverse events(AEs) | Up to approximately 2 years | Incidence and severity of AEs is aim to evaluate the safety of AK104 in combination with Chiauranib. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| duration of response (DoR) | Up to approximately 2 years | Duration of response (DoR) is defined as the period from the first documentation of confirmed response (CR or PR) to the first documentation of progressive disease(PD) (as per RECIST v1.1) or death due to any cause, whichever occurs first. |
| time to response (TTR) | Up to approximately 2 years | Time to response (TTR) is defined as the time from the first dose of investigational products until the first confirmation of CR or PR. |
| overall survival (OS) | Up to approximately 2 years | Overall survival (OS) is defined as the time from the first dose of investigational products until death due to any cause. |
| Pharmacokinetics(PK) profiles | Up to approximately 2 years | Serum concentrations of AK104 and plasma concentrations of Chiauranib in individual subjects at different time points after administration of AK104 in combination with Chiauranib. |
| Immunogenicity assessment | Up to approximately 2 years | The immunogenic potential of AK104 in combination with Chiauranib will be assessed by summarizing the number and percentage of subjects with detectable antidrug antibody(ADA). |
| progression-free survival (PFS) | Up to approximately 2 years | Progression-free survival (PFS) is defined as the time from the first dose of investigational products until documentation of PD (as per RECIST v1.1) or death due to any cause, whichever occurs first. |
| Disease control rate (DCR) | Up to approximately 2 years | Disease control rate (DCR) is defined as the proportion of subjects achieving a best of response(BOR) of confirmed CR and PR and stable disease(SD) per RECIST v1.1. |
Other
| Measure | Time frame | Description |
|---|---|---|
| alpha thalassemia/mental retardation X-linked(ATRX) gene mutation status | Up to approximately 2 years | The ATRX gene mutation status in peripheral blood will be determined, and its correlation with efficacy indicators such as ORR, PFS and OS will be analyzed. |
| SCLC subtype | Up to approximately 2 years | The expression of proteins related to SCLC subtype in tumor tissue samples will be detected by immunohistochemistry (IHC) and its correlation with efficacy will be analyzed. |
Countries
Australia, China
Outcome results
None listed