A Dose-escalation Study of LUNA18 in Patients With Locally Advanced or Metastatic Solid Tumors (With Expansion).

Locally Advanced or Metastatic Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05012618
• Other study ID #: LUN101JG
• Status: Recruiting
• Phase: Phase 1
• Start date: October 8, 2021
• Est. completion date: March 31, 2025

Study information

• Verified date: December 2023
• Source: Chugai Pharmaceutical
• Contact: Clinical trials information
• Phone: only use Email
• Email: clinical-trials[@]chugai-pharm.co.jp
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 195
• Est. completion date: March 31, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Locally Advanced or Metastatic Solid Tumors
• Neoplasms

Intervention

Drug:
• LUNA18
LUNA18 Capsule
• Cetuximab
Cetuximab as a IV infusion

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital	Chuo-Ku	Tokyo
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
United States	NEXT Oncology	Austin	Texas
United States	NEXT Virginia	Fairfax	Virginia
United States	South Texas Accelerated Research Therapeutics (START) Midwest	Grand Rapids	Michigan
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Wisconsin - Carbone Cancer Center	Madison	Wisconsin
United States	Renown Regional Medical Center	Reno	Nevada

Sponsors (1)

Lead Sponsor	Collaborator
Chugai Pharmaceutical

Countries where clinical trial is conducted

United States,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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]	Incidence and nature of dose-limiting toxicities (DLTs)	From Cycle 0 Day 1 until Cycle 1 Day 28 (Cycle 0 is 6-9 days, and Cycle 1 is 28 days)
Primary	Safety and tolerability of LUNA18 (Adverse Events) [Part A, AA, B, C, D and E]	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)	From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months)
Primary	Plasma concentrations of LUNA18 when administered as a single agent [Part A, AA] and in combination with other anti-cancer drugs [Part D]	Plasma concentrations of LUNA18	From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months)
Primary	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]	Maximum plasma concentration (Cmax) of LUNA18	From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months)
Primary	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]	Time to reach maximum plasma drug concentration (Tmax) of LUNA18	From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months)
Primary	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]	Area under the concentration versus time curve (AUC) of LUNA18	From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months)
Primary	Phosphorylation level of ERK protein (pERK) in tumor tissues [Part B]	Phosphorylation level of ERK protein (pERK) in tumor tissues biomarkers as applicable in tumor tissues	From screening until the time of clinical responses and/or the time of progressive disease (up to approximately 43 months), if feasible
Primary	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]	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)	From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first (up to approximately 43 months)
Secondary	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]	Objective response, defined as CR or PR as best overall response per RECIST v1.1	From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first (up to approximately 43 months)
Secondary	Preliminary anti-tumor activity of LUNA18 [Part A, AA, B, C, D and E]	Disease control, defined as CR, PR and stable disease (SD) per RECIST v1.1	From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first (up to approximately 43 months)
Secondary	Preliminary anti-tumor activity of LUNA18 [Part A, AA, B, C, D and E]	Duration of response (DoR), defined as the time from the first occurrence of a documented objective response to the time of the first documented disease progression per RECIST v1.1 or death from any cause, whichever occurs first	From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first (up to approximately 43 months)
Secondary	Preliminary anti-tumor activity of LUNA18 [Part A, AA, B, C, D and E]	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	From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first (up to approximately 43 months)
Secondary	Anti-drug antibody to LUNA18[Part A, AA, B, C, D and E]	Incidence of anti-LUNA18 antibodies	From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months)
Secondary	Plasma concentrations of LUNA18 [Part B, C and E]	Plasma concentrations of LUNA18	From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months)
Secondary	Phosphorylation level of ERK protein (pERK) in tumor tissues [Part A, AA, C, D, E]	Phosphorylation level of ERK protein (pERK) in tumor tissues biomarkers as applicable in tumor tissues	From screening until the time of clinical responses and/or the time of progressive disease (up to approximately 43 months), if feasible