Extensive Stage Small Cell Lung Cancer
Conditions
Brief summary
This study is a phase I, open-label, multicenter trial designed to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and antitumor activity of ALPS12 in patients with extensive-stage small cell lung cancer. The study consists of two parts: a dose-escalation part and an expansion part.
Interventions
DRUGALPS12
ALPS12 as an IV infusion
DRUGobinutuzumab
Obinutuzumab as an IV infusion
Sponsors
Chugai Pharmaceutical
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Aged \>18 years at time of informed consent * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1 * Histologically documented extensive stage small cell lung cancer * Disease recurrence documented after at least one prior systemic therapy. * Confirmed availability of representative archival tumor specimens or fresh tumor specimen. * Measurable disease per RECIST v.1.1. * Adequate hematologic and end organ function
Exclusion criteria
* Pregnant or breastfeeding, or intending to become pregnant or breastfeeding during the study * History or complication of clinically significant autoimmune disease * a positive HIV antibody test at screening * Active hepatitis B or hepatitis C * Prior treatment with anti-CD137 antibody drugs, anti-CD3 antibody drugs, and/or DLL3-targeted therapies * Patients who have received any investigational or approved anticancer therapy, including hormone therapy and/or radiotherapy, within 21 days prior to the first administration of the investigational drug. * History of Grade 4 immune-related adverse events caused by prior anti-PD-L1/PD-1 antibody drugs or anti-CTLA-4 antibody drugs (excluding asymptomatic elevations in serum amylase/lipase) * Patients who discontinued immunotherapy due to Grade 3 immune-related adverse events caused by prior anti-PD-L1/PD-1 antibody drugs or anti-CTLA-4 antibody drugs (excluding asymptomatic elevations in serum amylase/lipase), and/or patients who experienced Grade 3 immune-related adverse events caused by immunotherapy within 6 months prior to the first administration of the investigational drug * Patients who received a live attenuated vaccine within 4 weeks prior to the first administration of the investigational drug * History or clinical evidence of primary central nervous system (CNS) malignancy, symptomatic CNS metastases, CNS metastases requiring any anti tumor treatment, or leptomeningeal disease * Current or past CNS diseases (e.g., stroke, epilepsy, CNS vasculitis, neurodegenerative diseases)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All part : Adverse events of ALPS12[safety and tolerability] | From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 42 months) | Incidence, nature, and severity of AEs graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.5.0, and CRS and Immune effector cell-associated neurotoxicity syndrome (ICANS) graded according to the ASTCT Consensus Grading Criteria |
| Dose Escalation part : Dose-limiting toxicities (DLTs) and PK profile of ALPS12[safety and tolerability] | From Cycle 1 Day 1 to the administration of ALPS12 on Cycle 2 Day 1 (Cycle 1 is 21 days) | Nature and frequency of DLTs, AEs, PK and PD profiles |
| Dose Escalation part : Immunogenicity of ALPS12 | From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 42 months) | Incidence of ADAs to ALPS12 and potential correlation with PK parameters and safety |
| Expansion part : Preliminary anti-tumor activity of ALPS12 when administered at selected dose(s) based on tumor assessment in patients with extensive stage SCLC | From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 42 months) | Objective response, defined as a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1, as determined by the Investigators |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate(ORR)[preliminary efficacy] | From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 42 months) | ORR assessed per RECIST v.1.1 by the investigators. |
| Disease control [preliminary efficacy] | From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 42 months) | defined as the proportion of patients who have CR, PR, or stable disease (SD) as best overall response per RECIST v.1.1 as determined by the investigator. |
| Duration of response (DoR)[preliminary efficacy] | From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 42 months) | Duration of response (DoR), defined as the time from the first occurrence of CR or PR to progression disease (PD) or death from any cause (whichever occurs first), per the investigator according to RECIST v.1.1 |
| Progression-free survival (PFS)[preliminary efficacy] | From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 42 months) | Progression-free survival (PFS), defined as the time from administration of first study treatment to the first occurrence of disease progression or death from any cause, as determined by the investigator according to RECIST v.1.1 |
| Overall survival (OS)[preliminary efficacy] | From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 42 months) | Overall survival (OS), defined as the time from administration of first study treatment to death from any cause |
| Immunogenicity of obinutuzumab | From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 42 months) | Incidence of ADAs to obinutuzumab and potential correlation with PK parameters and safety |
| Maximum serum concentration (Cmax) and Area under the concentration time-curve (AUC) of ALPS12 with obinutuzumab[PK profile] | From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 42 months) | Serum ALPS12 concentration and its PK parameters including Cmax and AUC etc. |
| Adverse events of obinutuzumab[safety and tolerability] | From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 42 months) | Incidence, nature, and severity of adverse events graded according to NCI Common Terminology CTCAE v5.0, with severity of CRS determined according to the American Society for Transplantation and Cell Therapy (ASTCT) Consensus Grading Criteria(In parts with obinutuzumab premedication) |
Countries
Hong Kong, Japan, Taiwan
Contacts
CONTACTClinical trials information
STUDY_DIRECTORSponsor Chugai Pharmaceutical Co.Ltd
clinical-trials@chugai-pharm.co.jp
Outcome results
None listed