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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Locally Advanced or Metastatic Solid Tumors

Intervention / Treatment
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* Drug: LUNA18
* Drug: Cetuximab


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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 | 
| 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 |