Locally Advanced or Metastatic Solid Tumors
Conditions
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.
Interventions
DRUGLUNA18
LUNA18 Capsule
DRUGCetuximab
Cetuximab as a IV infusion
Sponsors
Chugai Pharmaceutical
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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 |
| 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Disease control, defined as CR, PR and stable disease (SD) 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 |
| 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 |
Countries
Japan, United States
Outcome results
None listed