A Dose-escalation Study of LUNA18 in Patients With Locally Advanced or Metastatic Solid Tumors (With Expansion).
- Conditions
- Locally Advanced or Metastatic Solid Tumors
- Interventions
- Registration Number
- NCT05012618
- Lead Sponsor
- Chugai Pharmaceutical
- Brief Summary
This is a Phase 1 dose-escalation and cohort expansion study that will evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary activity of LUNA18 when administered as a single agent or in combination with other anti-cancer drugs in patients with locally advanced or metastatic solid tumors.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 195
- Age >= 18 years at time of signing informed consent form
- ECOG performance status of 0 or 1
- Patients with a histologically or cytologically proven diagnosis of a locally advanced, recurrent, or metastatic incurable solid tumor for which standard therapy either does not exist or has proven ineffective or intolerable
- Patients with documented RAS alterations positive solid tumors
- Patients with measurable disease per RECIST v1.1
- Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (Class II or greater), unstable angina, or myocardial infarction within the previous 6 months or unstable arrhythmias within the previous 3 months
- Patients with primary central nervous system (CNS) malignancy, untreated CNS metastases requiring any anti-tumor treatment, or active CNS metastases
- Patients with current severe, uncontrolled systemic disease (including, but not limited to, clinically significant cardiovascular disease, pulmonary disease, or renal disease, ongoing or active infection)
- Patients with a history or complication of interstitial lung disease (ILD)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Biomarker part (Part B) LUNA18 Patients will receive LUNA18 capsule(s) at doses where the tolerability is confirmed in Part A Cohort expansion part (Part C) LUNA18 Patients will receive LUNA18 capsule(s) at the recommended dose Backfill part (Part AA) LUNA18 Patients will receive LUNA18 capsule(s) at doses where the tolerability is confirmed in Part A Cohort expansion part (Part E) LUNA18 Patients will receive LUNA18 capsule(s) in combination with cetuximab at the recommended dose Dose escalation part (Part A) LUNA18 Patients will receive LUNA18 capsule(s) at escalated doses Dose finding part (Part D) Cetuximab Patients will receive LUNA18 capsule(s) in combination with cetuximab at finding doses Cohort expansion part (Part E) Cetuximab Patients will receive LUNA18 capsule(s) in combination with cetuximab at the recommended dose Dose finding part (Part D) LUNA18 Patients will receive LUNA18 capsule(s) in combination with cetuximab at finding doses
- Primary Outcome Measures
Name Time Method Safety and tolerability of LUNA18 (Dose-limiting toxicities) when administered as a single agent [Part A] and in combination with other anti-cancer drugs [Part D] From Cycle 0 Day 1 until Cycle 1 Day 28 (Cycle 0 is 6-9 days, and Cycle 1 is 28 days) Incidence and nature of dose-limiting toxicities (DLTs)
Safety and tolerability of LUNA18 (Adverse Events) [Part A, AA, B, C, D and E] From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months) Incidence, nature and severity of adverse events, with severity determined per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0)
Plasma concentrations of LUNA18 when administered as a single agent [Part A, AA] and in combination with other anti-cancer drugs [Part D] From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months) Plasma concentrations of LUNA18
Maximum plasma concentration (Cmax) of LUNA18 when administered as a single agent [Part A, AA] and in combination with other anti-cancer drugs [Part D] From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months) Maximum plasma concentration (Cmax) of LUNA18
Time to reach maximum plasma drug concentration (Tmax) of LUNA18 when administered as a single agent [Part A, AA] and in combination with other anti-cancer drugs [Part D] From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months) Time to reach maximum plasma drug concentration (Tmax) of LUNA18
Area under the concentration versus time curve (AUC) of LUNA18 when administered as a single agent [Part A, AA] and in combination with other anti-cancer drugs [Part D] From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months) Area under the concentration versus time curve (AUC) of LUNA18
Phosphorylation level of ERK protein (pERK) in tumor tissues [Part B] From screening until the time of clinical responses and/or the time of progressive disease (up to approximately 43 months), if feasible Phosphorylation level of ERK protein (pERK) in tumor tissues biomarkers as applicable in tumor tissues
Preliminary anti-tumor activity of LUNA18 when administered as a single agent [Part B, C] and in combination with other anti-cancer drugs [Part E] From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first (up to approximately 43 months) Objective response, defined as a confirmed complete response (CR) or partial response (PR) as best overall response per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
- Secondary Outcome Measures
Name Time Method Preliminary anti-tumor activity of LUNA18 [Part A, AA, B, C, D and E] From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first (up to approximately 43 months) Progression free survival (PFS), defined as the time from the first study treatment to the first occurrence of progression per RECIST v1.1 or death from any cause, whichever occurs first
Plasma concentrations of LUNA18 [Part B, C and E] From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months) Plasma concentrations of LUNA18
Phosphorylation level of ERK protein (pERK) in tumor tissues [Part A, AA, C, D, E] From screening until the time of clinical responses and/or the time of progressive disease (up to approximately 43 months), if feasible Phosphorylation level of ERK protein (pERK) in tumor tissues biomarkers as applicable in tumor tissues
Preliminary anti-tumor activity of LUNA18 when administered as a single agent [Part A, Part AA] and in combination with other anti-cancer drugs [Part D] From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first (up to approximately 43 months) Objective response, defined as CR or PR as best overall response per RECIST v1.1
Anti-drug antibody to LUNA18[Part A, AA, B, C, D and E] From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months) Incidence of anti-LUNA18 antibodies
Trial Locations
- Locations (20)
University of California - Davis
🇺🇸Davis, California, United States
Beth Israel Deaconess
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
South Texas Accelerated Research Therapeutics (START) Midwest
🇺🇸Grand Rapids, Michigan, United States
Renown Regional Medical Center
🇺🇸Reno, Nevada, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Abramson Cancer Center at Pennsylvania Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Rhode Island Hospital-Comprehensive Cancer Center
🇺🇸Providence, Rhode Island, United States
NEXT Oncology
🇺🇸Austin, Texas, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
NEXT Virginia
🇺🇸Fairfax, Virginia, United States
University of Wisconsin - Carbone Cancer Center
🇺🇸Madison, Wisconsin, United States
Aichi Cancer Center
🇯🇵Nagoya, Aichi, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
Shizuoka Cancer Center
🇯🇵Nagaizumi, Shizuoka, Japan
National Cancer Center Hospital
🇯🇵Chuo-Ku, Tokyo, Japan
The Cancer Institute Hospital of JFCR
🇯🇵Koto-ku, Tokyo, Japan
National Hospital Organization Kyushu Cancer Center
🇯🇵Fukuoka, Japan
Osaka International Cancer Institute
🇯🇵Osaka, Japan