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

Official title

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

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.

Interventions

• Drug ROSE12
  ROSE12 as a IV infusion
• Drug Atezolizumab
  Atezolizumab as a IV infusion
• Drug Pembrolizumab
  Pembrolizumab as a IV infusion

Primary outcome measures

• 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) [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) [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) [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) [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) [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 or pembrolizumab (Part E and F) [Time frame: From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months)]

Secondary outcome measures (12)

• 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 or pembrolizumab (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 or pembrolizumab (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 or pembrolizumab (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 maximum serum concentration (Cmax) of pembrolizumab for PK profile when administered in combination with ROSE12 (Part F) [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) [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) [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) [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

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Japan · 9 centers

• Aichi Cancer Center — Nagoya
• National Cancer Center Hospital East — Kashiwa-shi
• Kanagawa Cancer Center — Yokohama
• Kansai Medical University Hospital — Hirakata-shi
• Osaka International Cancer Institute — Osaka
• Kindai University Hospital — Sakai-shi
• Shizuoka Cancer Center — Nagaizumi-chō
• National Cancer Center Hospital — Chuo-ku
• … and 1 more center

United States · 5 centers

• University of Pennsylvania Perelman Center for Advanced Medicine — Philadelphia
• Rhode Island Hospital — Providence
• SCRI Oncology Partners — Nashville
• MD Anderson Cancer Center — Houston
• NEXT Oncology — Fairfax

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 PMID 41513409

Identifiers

NCT: NCT05907980 · RSE101CT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗