A Phase I Study of ROSE12 Alone and in Combination With Other Anti-tumor Agents in Patients With Solid Tumors

Phase 1RecruitingNCT05907980

Chugai Pharmaceutical209 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

209

Conditions

Solid Tumor

Interventions

ROSE12DRUG

ROSE12 as a IV infusion

AtezolizumabDRUG

Atezolizumab as a IV infusion

PembrolizumabDRUG

Pembrolizumab as a IV infusion

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

* 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

Locations (14)

University of Pennsylvania Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, United States

RECRUITING

Rhode Island Hospital

Providence, Rhode Island, United States

Outcomes

Primary Outcomes

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)

Incidence and nature of dose-limiting toxicities (DLTs)

Time frame: From Cycle 1 Day 1 until Cycle 1 Day 21 (Cycle 1 is 21 days)

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)

Incidence, nature, and severity of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

Time frame: From screening until study completion, treatment discontinuation or post-treatment follow up, assessed up to the end of the study (approximate 43 months)

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)

The maximum serum concentration (Cmax) of ROSE12

Time frame: 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 for PK profile when administered as a single agent and in combination with atezolizumab or pembrolizumab (All Parts)

The minimum serum concentration (Cmin) of ROSE12

Time frame: 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 for PK profile when administered as a single agent and in combination with atezolizumab or pembrolizumab (All Parts)

The area under the concentration time-curve (AUC) of ROSE12

Time frame: 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)

Central Contacts

Clinical trials information

CONTACT

only use Email clinical-trials@chugai-pharm.co.jp

Data from ClinicalTrials.gov

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Secondary Outcomes

Preliminary anti-tumor activity of ROSE12 when administered as a single agent and in combination with atezolizumab (Part A, B, C and D)

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.

Time frame: From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months)

Preliminary anti-tumor activity of ROSE12 when administered as a single agent and in combination with atezolizumab or pembrolizumab (All Parts)

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.

Time frame: From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months)

Preliminary anti-tumor activity of ROSE12 when administered as a single agent and in combination with atezolizumab or pembrolizumab (All Parts)

Duration of objective response (DoR), defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1.

Time frame: From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months)

Preliminary anti-tumor activity of ROSE12 when administered as a single agent and in combination with atezolizumab or pembrolizumab (All Parts)

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 v1.1.

Time frame: From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months)

The maximum serum concentration (Cmax) of atezolizumab for PK profile when administered in combination with ROSE12 (Part C, D and E)

The maximum serum concentration (Cmax) of atezolizumab

Time frame: 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 for PK profile when administered in combination with ROSE12 (Part C, D and E)

The minimum serum concentration (Cmin) of atezolizumab

Time frame: 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 for PK profile when administered in combination with ROSE12 (Part C, D and E)

The area under the concentration-time curve (AUC) of atezolizumab

Time frame: 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 pembrolizumab for PK profile when administered in combination with ROSE12 (Part F)

The maximum serum concentration (Cmax) of pembrolizumab

Time frame: 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 for PK profile when administered in combination with ROSE12 (Part F)

The minimum serum concentration (Cmin) of pembrolizumab

Time frame: 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 for PK profile when administered in combination with ROSE12 (Part F)

The area under the concentration-time curve (AUC) of pembrolizumab

Time frame: 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 immunogenicity of ROSE12 when administered as a single agent and in combination with atezolizumab or pembrolizumab (All Parts)

Prevalence and incidence of anti-drug antibodies (ADAs) to ROSE12 and potential correlation with PK parameters and safety

Time frame: 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 immunogenicity of atezolizumab when administered in combination with ROSE12 (Part C, D and E)

Prevalence and incidence of ADAs to atezolizumab and potential correlation with PK parameters and safety

Time frame: 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 immunogenicity of pembrolizumab when administered in combination with ROSE12 (Part F)

Prevalence and incidence of ADAs to pembrolizumab and potential correlation with PK parameters and safety

Time frame: 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)