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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced or Metastatic Solid Tumors
• Intervention / Treatment: Drug: LUNA18; Drug: Cetuximab

• Study Type: Interventional
• Enrollment (Estimated): 195
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical trials information; Phone Number: only use Email; Email: clinical-trials@chugai-pharm.co.jp

Study Locations

• Japan
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • Recruiting
      • National Cancer Center Hospital East
  • Tokyo
    • Chuo-Ku, Tokyo, Japan, 104-0045
      • Recruiting
      • National Cancer Center Hospital
• United States
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Recruiting
      • South Texas Accelerated Research Therapeutics (START) Midwest
  • Nevada
    • Reno, Nevada, United States, 89502
      • Recruiting
      • Renown Regional Medical Center
  • Texas
    • Austin, Texas, United States, 78758
      • Recruiting
      • NEXT Oncology
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Next Virginia
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Recruiting
      • University of Wisconsin - Carbone Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation part (Part A); Patients will receive LUNA18 capsule(s) at escalated doses	Drug: LUNA18; LUNA18 Capsule
Experimental: Biomarker part (Part B); Patients will receive LUNA18 capsule(s) at doses where the tolerability is confirmed in Part A	Drug: LUNA18; LUNA18 Capsule
Experimental: Cohort expansion part (Part C); Patients will receive LUNA18 capsule(s) at the recommended dose	Drug: LUNA18; LUNA18 Capsule
Experimental: Backfill part (Part AA); Patients will receive LUNA18 capsule(s) at doses where the tolerability is confirmed in Part A	Drug: LUNA18; LUNA18 Capsule
Experimental: Dose finding part (Part D); Patients will receive LUNA18 capsule(s) in combination with cetuximab at finding doses	Drug: LUNA18; LUNA18 Capsule; Drug: Cetuximab; Cetuximab as a IV infusion
Experimental: Cohort expansion part (Part E); Patients will receive LUNA18 capsule(s) in combination with cetuximab at the recommended dose	Drug: LUNA18; LUNA18 Capsule; Drug: Cetuximab; Cetuximab as a IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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)
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)
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)
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)
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)
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)
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)
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)
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)
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

Collaborators and Investigators

• Sponsor: Chugai Pharmaceutical
• Investigators: Study Director: Sponsor Chugai Pharmaceutical Co. Ltd, clinical-trials@chugai-pharm.co.jp

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2021
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: August 3, 2021
• First Submitted That Met QC Criteria: August 12, 2021
• First Posted (Actual): August 19, 2021

Study Record Updates

• Last Update Posted (Actual): December 8, 2023
• Last Update Submitted That Met QC Criteria: December 3, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: LUN101JG

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). For further details on Chugai's Data Sharing Policy and how to request access to related clinical study documents, see here (www.chugai-pharm.co.jp/english/profile/rd/ctds_request.html).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No