RecruitingInterventionalPhase 1

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

NCT ID: NCT05907980Sponsor: Chugai PharmaceuticalLast updated: 2025-03-06

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.

Arms & interventions

DrugROSE12
ROSE12 as a IV infusion
DrugAtezolizumab
Atezolizumab as a IV infusion

Outcome measures

Primary

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 (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 (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 (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 (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)
Preliminary anti-tumor activity of ROSE12 when administered in combination with atezolizumab (Part E)
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
Time frame: From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months)

Secondary

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

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy 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) 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 locations (2)

MD Anderson Cancer Center

Houston, Texas, 77030

Recruiting

NEXT Oncology

Fairfax, Virginia, 22031

Recruiting

References

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.(PubMed)