Title
A Phase I Open-Label, Dose-Escalation and Cohort Expansion Study of LUNA18 Monotherapy and Combination Therapy in Patients With Locally Advanced or Metastatic Solid Tumors

Description
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

Objective
Primary Objectives:

Part A (LUNA18 monotherapy dose escalation cohorts), Part AA (LUNA18 monotherapy backfill cohorts) and Part D (LUNA18 combination dose finding cohorts):
-To evaluate the safety and tolerability of LUNA18 when administered as a single agent (Part A, Part AA) and in combination with other anti-cancer drugs (Part D)
-To determine the maximum tolerated dose (MTD) and the recommended dose (RD) when administered as a single agent (Part A) and in combination with other anticancer drugs (Part D)
-To characterize the PK profile of LUNA18 in plasma when administered as a single agent (Part A, Part AA) and in combination with other anti-cancer drugs (Part D)

Part B (LUNA18 monotherapy biomarker cohorts):
-To evaluate the safety and tolerability of LUNA18
-To evaluate the inhibition of the phosphorylation level of extracellular signal-regulated kinase (ERK) protein (pERK) and other biomarkers as applicable in tumor tissues
-To evaluate the preliminary anti-tumor activity of LUNA18

Part C (LUNA18 monotherapy expansion cohorts) and Part E (LUNA18 combination expansion cohorts):
-To evaluate the safety and tolerability of LUNA18 when administered as a single agent (Part C) and in combination with other anti-cancer drugs (Part E)
-To evaluate the preliminary anti-tumor activity of LUNA18 when administered as a single agent (Part C) and in combination with other anti-cancer drugs (Part E)

Secondary Objectives:

Part A (LUNA18 monotherapy dose escalation cohorts), Part AA (LUNA18 monotherapy backfill cohorts) and Part D (LUNA18 combination dose finding cohorts):
-To evaluate the 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)
-To evaluate the immunogenicity of LUNA18 when administered as a single agent (Part A, Part AA) and in combination with other anti-cancer drugs (Part D)
-To evaluate the inhibition of the phosphorylation level of pERK and other biomarkers as applicable in tumor tissues when administered as a single agent (Part A, Part AA) and in combination with other anti-cancer drugs (Part D)
-To evaluate the difference of LUNA18 PK between hard capsule and soft capsule (Part A, Part AA)
-To evaluate the difference of LUNA18 PK between monotherapy (Part A, Part AA) and combination therapy (Part D)
-To characterize PK profile and immunogenicity of other anti-cancer drugs when administered in combination with LUNA18 (Part D)

Part B (LUNA18 monotherapy biomarker cohorts):
-To evaluate the additional preliminary anti-tumor activity of LUNA18
-To characterize the PK profile and to evaluate the immunogenicity of LUNA18

Part C (LUNA18 monotherapy expansion cohorts) and Part E (LUNA18 combination expansion cohorts):
-To evaluate the additional preliminary anti-tumor activity of LUNA18 when administered as a single agent (Part C) and in combination with other anti-cancer drugs (Part E)
-To characterize PK profile and to evaluate the immunogenicity of LUNA18 when administered as a single agent (Part C) and in combination with other anti-cancer drugs (Part E)
-To evaluate the inhibition of the phosphorylation level of pERK and other biomarkers as applicable in tumor tissues when administered as a single agent (Part C) and in combination with other anti-cancer drugs (Part E)
-To characterize PK profile and immunogenicity of other anti-cancer drugs when administered in combination with LUNA18 (Part E)

Treatment 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.

Key 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

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)

Applicable Disease Sites
Anal; Any Site; Bladder; Brain/Central Nervous System; Breast; Cervix; Colon and Rectum; Endocrine cancers; Esophagus; Gastrointestinal cancers, other; Genitourinary cancers, other; Head and Neck; Ill-Defined Sites; Kidney; Liver; Lung; Melanoma/Skin cancer; Ovary; Pancreas; Prostate; Sarcoma; Stomach; Thyroid; Unknown Sites; Uterus

Participating Institutions
UW Health 1 S. Park Medical Center; UW Health Eastpark Medical Center; UW Health University Hospital