Solid Tumor
Conditions
Brief summary
This is a Phase Ia/Ib open-label, dose-escalation study to evaluate the safety and pharmacokinetics of ROSE12 as a single agent and in combination with other anti-tumor agents in patients with locally advanced or metastatic solid tumors. The study will consist of three parts: a dose-escalation part, a biopsy part (the part to evaluate biomarkers), and an expansion part.
Interventions
DRUGROSE12
ROSE12 as a IV infusion
DRUGAtezolizumab
Atezolizumab as a IV infusion
DRUGPembrolizumab
Pembrolizumab as a 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
* Age \>= 18 years at time of signing informed consent form (ICF) * Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1 * Adequate hematologic and end-organ function * Life expectancy \>= 12 weeks * Patients with histologic documentation of locally advanced, or metastatic solid tumor * \[Dose-escalation Parts and Biopsy Parts\]Refractory or resistant to standard therapies or standard therapies are not available * \[Dose-escalation Parts and Expansion Part\] Patients with confirmed availability of fresh tumor or representative tumor specimens * \[Biopsy Parts\] Patients with accessible lesion(s) * \[Expansion Parts\] Patients with ICI (immune checkpoint inhibitor)-refractory 2L-3L NSCLC (non-small-cell lung cancer) and 3L+ CRC (colorectal cancer)
Exclusion criteria
* Clinically significant cardiovascular or liver disease * Treatment with investigational therapy and anti-cancer therapy within 28 days prior to initiation of study drug * Any history of an immune-mediated Grade 4 adverse event attributed to prior cancer immunotherapy (other than asymptomatic elevation of serum amylase or lipase). * All imAEs from prior cancer immunotherapy (other than endocrinopathy managed with replacement therapy, stable vitiligo or stable alopecia) that have not resolved completely to baseline. * Adverse events from prior anti-cancer therapy that have not resolved to Grade ≤ 1 except for alopecia, vitiligo, or endocrinopathy managed with replacement therapy * Primary central nervous system (CNS) malignancy, untreated CNS metastases requiring any anti-tumor treatment, or active CNS metastases * Uncontrolled tumor-related pain * Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures * Active or history of clinically significant autoimmune disease * History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins. \[Expansion Part\] * Prior treatment with investigational product which has MoA of Treg depletion * Malignancies other than disease under study within 5 years prior to Cycle 1 Day 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The maximum tolerated dose (MTD) and the recommended dose (RD) of ROSE12 when administered as a single agent and in combination with atezolizumab (Part A and C) | From Cycle 1 Day 1 until Cycle 1 Day 21 (Cycle 1 is 21 days) | Incidence and nature of dose-limiting toxicities (DLTs) |
| Safety (All Parts) and tolerability (Part A, B, C and D) of ROSE12 when administered as a single agent and in combination with atezolizumab or pembrolizumab (Adverse Events) | From screening until study completion, treatment discontinuation or post-treatment follow up, assessed up to the end of the study (approximate 43 months) | Incidence, nature, and severity of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 |
| The maximum serum concentration (Cmax) of ROSE12 for PK profile when administered as a single agent and in combination with atezolizumab or pembrolizumab (All Parts) | From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months) | The maximum serum concentration (Cmax) of ROSE12 |
| The minimum serum concentration (Cmin) of ROSE12 for PK profile when administered as a single agent and in combination with atezolizumab or pembrolizumab (All Parts) | From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months) | The minimum serum concentration (Cmin) of ROSE12 |
| The area under the concentration time-curve (AUC) of ROSE12 for PK profile when administered as a single agent and in combination with atezolizumab or pembrolizumab (All Parts) | From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months) | The area under the concentration time-curve (AUC) of ROSE12 |
| Preliminary anti-tumor activity of ROSE12 when administered in combination with atezolizumab or pembrolizumab (Part E and F) | From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months) | Objective response rate (ORR), defined as the proportion of patients with an objective response (complete response \[CR\] or partial response \[PR\]) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to the Response Evaluation Criteria in Solid Tumors version 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Preliminary anti-tumor activity of ROSE12 when administered as a single agent and in combination with atezolizumab (Part A, B, C and D) | From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months) | ORR, defined as the proportion of patients with an objective response on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. |
| Preliminary anti-tumor activity of ROSE12 when administered as a single agent and in combination with atezolizumab or pembrolizumab (All Parts) | From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months) | Disease control rate (DCR), defined as the proportion of patients who had an objective response or stable disease (SD) which is confirmed no less than 6 weeks after the start of treatment as the minimum duration, as determined by the investigator with use of RECIST v1.1. |
| The maximum serum concentration (Cmax) of atezolizumab for PK profile when administered in combination with ROSE12 (Part C, D and E) | From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months) | The maximum serum concentration (Cmax) of atezolizumab |
| The minimum serum concentration (Cmin) of atezolizumab for PK profile when administered in combination with ROSE12 (Part C, D and E) | From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months) | The minimum serum concentration (Cmin) of atezolizumab |
| The area under the concentration-time curve (AUC) of atezolizumab for PK profile when administered in combination with ROSE12 (Part C, D and E) | From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months) | The area under the concentration-time curve (AUC) of atezolizumab |
| The maximum serum concentration (Cmax) of pembrolizumab for PK profile when administered in combination with ROSE12 (Part F) | From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 24 months) | The maximum serum concentration (Cmax) of pembrolizumab |
| The minimum serum concentration (Cmin) of pembrolizumab for PK profile when administered in combination with ROSE12 (Part F) | From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 24 months) | The minimum serum concentration (Cmin) of pembrolizumab |
| The area under the concentration-time curve (AUC) of pembrolizumab for PK profile when administered in combination with ROSE12 (Part F) | From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 24 months) | The area under the concentration-time curve (AUC) of pembrolizumab |
| The immunogenicity of ROSE12 when administered as a single agent and in combination with atezolizumab or pembrolizumab (All Parts) | From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months) | Prevalence and incidence of anti-drug antibodies (ADAs) to ROSE12 and potential correlation with PK parameters and safety |
| The immunogenicity of atezolizumab when administered in combination with ROSE12 (Part C, D and E) | From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months) | Prevalence and incidence of ADAs to atezolizumab and potential correlation with PK parameters and safety |
| The immunogenicity of pembrolizumab when administered in combination with ROSE12 (Part F) | From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months) | Prevalence and incidence of ADAs to pembrolizumab and potential correlation with PK parameters and safety |
Countries
Japan, United States
Contacts
CONTACTClinical trials information
STUDY_DIRECTORSponsor Chugai Pharmaceutical Co.Ltd
clinical-trials@chugai-pharm.co.jp
Outcome results
None listed