Locally Advanced or Metastatic Solid Tumors
Conditions
Brief summary
Phase I, open-label, multi-center study
Interventions
DRUGSPYK04
SPYK04 capsule
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
(Both Part I and Part II) * Age \>= 18 years at time of signing informed consent form * ECOG performance status of 0 or 1 * Patients with a locally advanced, recurrent, or metastatic solid tumor for which standard therapy either does not exist or has proven ineffective or intolerable (Part I only) * Patients with measurable and/or evaluable disease per RECIST v1.1 * Patients with MAPK pathway alterations positive solid tumor (i.e., BRAF, K/N/H-RAS mutations) (Part II only) * Patients with measurable disease per RECIST v1.1 * Patients with KRAS mutated NSCLC (NSCLC cohort) * Patients with KRAS mutated Ovarian Cancer (Ovarian Cancer cohort) * Patients with RAS mutated solid tumor (Biopsy cohort)
Exclusion criteria
(Both Part I and Part II) * 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 |
|---|---|---|
| Safety and tolerability of SPYK04 (Dose limiting toxicities) [Dose escalation] | From first dose until the end of Cycle 1 (approximately 35 days) | Incidence and nature of DLTs |
| Safety and tolerability of SPYK04 (Adverse Events) [Dose escalation] | From Cycle 0 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion) | Incidence, nature, and severity of adverse events (AEs) as assessed by the NCI CTCAE v5.0 |
| Safety and tolerability of SPYK04 (Electrocardiograms in triplicate) [Dose escalation] | From first dose until the end of Cycle 1 (approximately 35 days) | Uncorrected QT interval, QTcF, PR duration, QRS interval and RR interval |
| Pharmacokinetics of SPYK04 [Dose escalation] | From Cycle 0 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion) | Plasma concentrations of SPYK04 |
| Preliminary anti-tumor activity of SPYK04 [Cohort expansion] | From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to 42 months (study completion) | Objective Response Rate (ORR) is defined as proportion of patients who had a confirmed complete response (CR) or partial response (PR), as determined by the investigator with use of Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Preliminary anti-tumor activity of SPYK04 [Dose escalation] | From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to 42 months (study completion) | Objective Response |
| Safety and tolerability of SPYK04 (AEs) [Cohort expansion] | From Cycle 1 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion) | Incidence, nature, and severity of AEs assessed by the NCI CTCAE v5.0 |
| Preliminary anti-tumor activity of SPYK04 [Cohort expansion] | From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to 42 months (study completion) | Disease control rate (DCR) is defined as proportion of patients who had an objective response or stable disease (SD), as determined by the investigator with use of RECIST v1.1 |
| Pharmacokinetics of SPYK04 [Cohort expansion] | From Cycle 1 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion) | Plasma concentrations of SPYK04 |
| Pharmacodynamics of SPYK04 [Cohort expansion] | From screening until the time of partial response or stable disease lasting for more than 4 months, and the time of progressive disease, if possible, an average of 1 year | Expression level of pMEK and pERK in solid tumor tissues (e.g., baseline archival or biopsy, and on treatment biopsy) |
Countries
Japan, United States
Contacts
STUDY_DIRECTORSponsor Chugai Pharmaceutical Co. Ltd
clinical-trials@chugai-pharm.co.jp
Outcome results
None listed