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

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

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 Overview

• Status: Recruiting
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: ROSE12; Drug: Atezolizumab; Drug: Pembrolizumab

• Study Type: Interventional
• Enrollment (Estimated): 209
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical trials information; Phone Number: only use Email; Email: clinical-trials@chugai-pharm.co.jp

Study Locations

• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 464-8681
      • Recruiting
      • Aichi Cancer Center
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • Recruiting
      • National Cancer Center Hospital East
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 241-8515
      • Recruiting
      • Kanagawa Cancer Center
  • Osaka
    • Hirakata-shi, Osaka, Japan, 573-1191
      • Recruiting
      • Kansai Medical University Hospital
    • Osaka, Osaka, Japan, 541-8567
      • Recruiting
      • Osaka International Cancer Institute
    • Sakai-shi, Osaka, Japan, 590-0197
      • Recruiting
      • Kindai University Hospital
  • Shizuoka
    • Nagaizumi-chō, Shizuoka, Japan, 411-8777
      • Recruiting
      • Shizuoka Cancer Center
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • Recruiting
      • National Cancer Center Hospital
    • Koto-Ku, Tokyo, Japan, 135-8550
      • Recruiting
      • The Cancer Institute Hospital Of JFCR
• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania Perelman Center for Advanced Medicine
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Recruiting
      • Rhode Island Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • SCRI Oncology Partners
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • NEXT Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Dose-escalation part of Phase Ia; Patients will receive ROSE12 as a IV infusion at escalated doses.	Drug: ROSE12; ROSE12 as a IV infusion
Experimental: Part B: Biopsy part of Phase Ia; Serial biopsy will be conducted with patients who will receive ROSE12 as a IV infusion at escalated doses.	Drug: ROSE12; ROSE12 as a IV infusion
Experimental: Part C: Dose-escalation part of Phase Ib; Patients will receive ROSE12 and atezolizumab as a IV infusion at escalated doses.	Drug: ROSE12; ROSE12 as a IV infusion; Drug: Atezolizumab; Atezolizumab as a IV infusion
Experimental: Part D: Biopsy part of Phase Ib; Serial biopsy will be conducted with patients who will receive ROSE12 and atezolizumab as a IV infusion at escalated doses.	Drug: ROSE12; ROSE12 as a IV infusion; Drug: Atezolizumab; Atezolizumab as a IV infusion
Experimental: Part E: Expansion part of Phase Ib in patients with selected solid tumors; Patients will receive ROSE12 and atezolizumab as a IV infusion at the recommended dose.	Drug: ROSE12; ROSE12 as a IV infusion; Drug: Atezolizumab; Atezolizumab as a IV infusion
Experimental: Part F: Expansion part of Phase Ib in patients with selected solid tumors; Patients will receive ROSE12 and pembrolizumab as a IV infusion at the recommended dose.	Drug: ROSE12; ROSE12 as a IV infusion; Drug: Pembrolizumab; Pembrolizumab as a IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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	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	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	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	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)
Preliminary anti-tumor activity of ROSE12 when administered in combination with atezolizumab or pembrolizumab (Part E and F)	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	From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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	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	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	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	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)
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.	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.	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.	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 pembrolizumab for PK profile when administered in combination with ROSE12 (Part F)	The maximum serum concentration (Cmax) of pembrolizumab	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	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	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	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	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)

Collaborators and Investigators

• Sponsor: Chugai Pharmaceutical
• Investigators: Study Director: Sponsor Chugai Pharmaceutical Co.Ltd, clinical-trials@chugai-pharm.co.jp

Publications and helpful links

General Publications

• Hayashi H, Tatsumi K, Katada H, Matsuda Y, Tsunenari T, Honda M, Nemoto T, Shimizu S, Miura-Okuda M, Ikuta Y, Ito A, Ogami C, Kato C, Kamimura M, Kibayashi T, Kubo C, Komatsu S, Komori Y, Shinozuka J, Susumu H, Tanno H, Tomii Y, Nakagawa K, Nagano H, Nanami M, Nishito Y, Fujisawa N, Matsushita T, Michisaka S, Yamazaki M, Yoshimoto M, Wakatsuki H, Wakabayashi T, Wada NA, Ueda O, Konishi H, Kashima K, Tanaka H, Endo M, Kitazawa T, Sakaguchi S, Kamata-Sakurai M, Igawa T. ROSE12, a novel anti-CTLA-4 FcgammaRs binding-enhanced antibody activated by extracellular adenosine triphosphate, shows tumor-selective regulatory T-cell depletion and antitumor efficacy without systemic immune activation. J Immunother Cancer. 2026 Jan 9;14(1):e013397. doi: 10.1136/jitc-2025-013397.

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2023
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: April 20, 2023
• First Submitted That Met QC Criteria: June 14, 2023
• First Posted (Actual): June 18, 2023

Study Record Updates

• Last Update Posted (Actual): July 28, 2026
• Last Update Submitted That Met QC Criteria: July 26, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab; atezolizumab
• Other Study ID Numbers: RSE101CT

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No