A Dose-escalation Study of LUNA18 in Patients With Locally Advanced or Metastatic Solid Tumors (With Expansion).
Study Details
Study Description
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 in patients with locally advanced or metastatic solid tumors.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- Safety and tolerability of LUNA18 (Dose-limiting toxicities) [Part A] [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, B and C] [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 [Part A] [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 [Part A] [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 [Part A] [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 [Part A] [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 [Part C] [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
- Preliminary anti-tumor activity of LUNA18 [Part A] [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
- Preliminary anti-tumor activity of LUNA18 [Part A, B and C] [From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first (up to approximately 43 months)]
Disease control, defined as CR, PR and stable disease (SD) per RECIST v1.1
- Preliminary anti-tumor activity of LUNA18 [Part A, B and C] [From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first (up to approximately 43 months)]
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
- Preliminary anti-tumor activity of LUNA18 [Part A, B and C] [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
- Anti-drug antibody to LUNA18 [Part A, B and C] [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
- Plasma concentrations of LUNA18 [Part B and C] [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 and C] [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
Eligibility Criteria
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)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | NEXT Oncology | Austin | Texas | United States | 78758 |
| 2 | MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 3 | National Cancer Center Hospital East | Kashiwa | Chiba | Japan | 277-8577 |
| 4 | National Cancer Center Hospital | Chuo-Ku | Tokyo | Japan | 104-0045 |
Sponsors and Collaborators
- Chugai Pharmaceutical
Investigators
- Study Director: Sponsor Chugai Pharmaceutical Co. Ltd, clinical-trials@chugai-pharm.co.jp
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- LUN101JG