A Dose-Escalation Study of SPYK04 in Patients With Locally Advanced or Metastatic Solid Tumors (With Expansion).

Phase 1Active Not RecruitingNCT04511845

Chugai Pharmaceutical113 enrolled

Overview

Phase I, open-label, multi-center study

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

113

Conditions

Locally Advanced or Metastatic Solid Tumors

Interventions

SPYK04DRUG

SPYK04 capsule

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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)

Locations (15)

Arizona Oncology

Tucson, Arizona, United States

Rocky Mountain Cancer Centers

Lone Tree, Colorado, United States

Outcomes

Primary Outcomes

Safety and tolerability of SPYK04 (Dose limiting toxicities) [Dose escalation]

Incidence and nature of DLTs

Time frame: From first dose until the end of Cycle 1 (approximately 35 days)

Safety and tolerability of SPYK04 (Adverse Events) [Dose escalation]

Incidence, nature, and severity of adverse events (AEs) as assessed by the NCI CTCAE v5.0

Time frame: From Cycle 0 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion)

Safety and tolerability of SPYK04 (Electrocardiograms in triplicate) [Dose escalation]

Uncorrected QT interval, QTcF, PR duration, QRS interval and RR interval

Time frame: From first dose until the end of Cycle 1 (approximately 35 days)

Safety and tolerability of SPYK04 (Electrocardiograms in triplicate) [Dose escalation]

Heart Rate

Time frame: From first dose until the end of Cycle 1 (approximately 35 days)

Pharmacokinetics of SPYK04 [Dose escalation]

Plasma concentrations of SPYK04

Time frame: From Cycle 0 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion)

Pharmacokinetics of SPYK04 [Dose escalation]

Maximum plasma concentration (Cmax) of SPYK04

Time frame: From Cycle 0 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion)

Pharmacokinetics of SPYK04 [Dose escalation]

Time to reach maximum plasma drug concentration (Tmax) of SPYK04

Time frame: From Cycle 0 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion)

Data from ClinicalTrials.gov

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Secondary Outcomes

Preliminary anti-tumor activity of SPYK04 [Dose escalation]

Objective Response

Time frame: From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to 42 months (study completion)

Safety and tolerability of SPYK04 (AEs) [Cohort expansion]

Incidence, nature, and severity of AEs assessed by the NCI CTCAE v5.0

Time frame: From Cycle 1 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion)

Preliminary anti-tumor activity of SPYK04 [Cohort expansion]

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

Time frame: From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to 42 months (study completion)

Preliminary anti-tumor activity of SPYK04 [Cohort expansion]

Progression-free survival (PFS) is defined as the time from the first study treatment to the first occurrence of progression as determined by the investigator using RECIST v1.1 or death from any cause, whichever occurs first

Time frame: From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to 42 months (study completion)

Preliminary anti-tumor activity of SPYK04 [Cohort expansion]

Duration of response (DoR) is defined for patients with a CR or PR at the time from the first documented CR or PR to documented disease progression as determined by the investigator with use of RECIST v1.1 or death from any cause, whichever occurs first

Time frame: From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to 42 months (study completion)

Pharmacokinetics of SPYK04 [Cohort expansion]

Plasma concentrations of SPYK04

Time frame: From Cycle 1 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion)

Pharmacokinetics of SPYK04 [Cohort expansion]

Maximum plasma concentration (Cmax) of SPYK04

Time frame: From Cycle 1 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion)

Pharmacokinetics of SPYK04 [Cohort expansion]

Time to reach maximum plasma drug concentration (Tmax) of SPYK04

Time frame: From Cycle 1 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion)

Pharmacokinetics of SPYK04 [Cohort expansion]

Area under the concentration versus time curve (AUC) of SPYK04

Time frame: From Cycle 1 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion)

Pharmacodynamics of SPYK04 [Cohort expansion]

Expression level of pMEK and pERK in solid tumor tissues (e.g., baseline archival or biopsy, and on treatment biopsy)

Time frame: 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