Clinical trial NCT05012618: A Dose-escalation Study of LUNA18 in Patients With Locally Advanced or Metastatic Solid Tumors (With Expansion).
Official title: A Phase 1 Open-label, Dose-escalation and Cohort Expansion Study of LUNA18 Monotherapy and Combination Therapy in Patients With Locally Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Locally Advanced or Metastatic Solid Tumors
Lead sponsor: Chugai Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2021-08-19
Enrollment: 195
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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)

Primary outcomes:
measure: 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]
timeFrame: From Cycle 0 Day 1 until Cycle 1 Day 28 (Cycle 0 is 6-9 days, and Cycle 1 is 28 days)
measure: Safety and tolerability of LUNA18 (Adverse Events) [Part A, AA, B, C, D and E]
timeFrame: From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months)
measure: Plasma concentrations of LUNA18 when administered as a single agent [Part A, AA] and in combination with other anti-cancer drugs [Part D]
timeFrame: From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months)
measure: 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]
timeFrame: From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months)
measure: 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]
timeFrame: From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months)
measure: 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]
timeFrame: From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months)
measure: Phosphorylation level of ERK protein (pERK) in tumor tissues [Part B]
timeFrame: From screening until the time of clinical responses and/or the time of progressive disease (up to approximately 43 months), if feasible
measure: 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]
timeFrame: From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first (up to approximately 43 months)
Secondary outcomes:
measure: 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]
timeFrame: From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first (up to approximately 43 months)
measure: Preliminary anti-tumor activity of LUNA18 [Part A, AA, B, C, D and E]
timeFrame: From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first (up to approximately 43 months)
measure: Preliminary anti-tumor activity of LUNA18 [Part A, AA, B, C, D and E]
timeFrame: From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first (up to approximately 43 months)
measure: Preliminary anti-tumor activity of LUNA18 [Part A, AA, B, C, D and E]
timeFrame: From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first (up to approximately 43 months)
measure: Anti-drug antibody to LUNA18[Part A, AA, B, C, D and E]
timeFrame: From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months)
measure: Plasma concentrations of LUNA18 [Part B, C and E]
timeFrame: From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months)
measure: Phosphorylation level of ERK protein (pERK) in tumor tissues [Part A, AA, C, D, E]
timeFrame: From screening until the time of clinical responses and/or the time of progressive disease (up to approximately 43 months), if feasible
Other outcomes:
Locations:
city: Davis
country: United States
facility: University of California - Davis
state: California
city: Boston
country: United States
facility: Beth Israel Deaconess
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Grand Rapids
country: United States
facility: South Texas Accelerated Research Therapeutics (START) Midwest
state: Michigan
city: Reno
country: United States
facility: Renown Regional Medical Center
state: Nevada
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Philadelphia
country: United States
facility: Abramson Cancer Center at Pennsylvania Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital-Comprehensive Cancer Center
state: Rhode Island
city: Austin
country: United States
facility: NEXT Oncology
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin - Carbone Cancer Center
state: Wisconsin
city: Nagoya
country: Japan
facility: Aichi Cancer Center
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Nagaizumi
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka
city: Chuo-Ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Koto-ku
country: Japan
facility: The Cancer Institute Hospital of JFCR
state: Tokyo
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
Study officials:
affiliation: clinical-trials@chugai-pharm.co.jp
name: Sponsor Chugai Pharmaceutical Co. Ltd
role: STUDY_DIRECTOR
References: