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

Locally Advanced or Metastatic Solid Tumors Clinical Trial

Official title:

A Phase I, Open-Label, Multicenter, Dose Escalation and Cohort Expansion Study of SPYK04 as Monotherapy in Patients With Locally Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04511845
• Other study ID #: SPK101JG
• Status: Recruiting
• Phase: Phase 1
• Start date: September 10, 2020
• Est. completion date: September 30, 2024

Study information

• Verified date: October 2023
• Source: Chugai Pharmaceutical
• Contact: Clinical trials information
• Phone: only use Email
• Email: clinical-trials[@]chugai-pharm.co.jp
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Phase I, open-label, multi-center study

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 113
• Est. completion date: September 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Locally Advanced or Metastatic Solid Tumors
• Neoplasms

Intervention

Drug:
• SPYK04
SPYK04 capsule

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital	Chuo Ku	Tokyo
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	Cancer Institute Hospital of Japanese Foundation for Cancer Research	Koto-Ku	Tokyo
Japan	Kurume University Hospital	Kurume	Fukuoka
Japan	Osaka Prefectural Hospital Organization Osaka International Cancer Center	Osaka
United States	University of Virginia	Charlottesville	Virginia
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	MD Anderson Cancer Center	Houston	Texas
United States	Rocky Mountain Cancer Centers	Lone Tree	Colorado
United States	Froedtert Hospital and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Minnesota Oncology	Minneapolis	Minnesota
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Arizona Oncology	Tucson	Arizona
United States	Texas Oncology	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Chugai Pharmaceutical

Countries where clinical trial is conducted

United States,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of SPYK04 (Dose limiting toxicities) [Dose escalation]	Incidence and nature of DLTs	From first dose until the end of Cycle 1 (approximately 35 days)
Primary	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	From Cycle 0 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion)
Primary	Safety and tolerability of SPYK04 (Electrocardiograms in triplicate) [Dose escalation]	Uncorrected QT interval, QTcF, PR duration, QRS interval and RR interval	From first dose until the end of Cycle 1 (approximately 35 days)
Primary	Safety and tolerability of SPYK04 (Electrocardiograms in triplicate) [Dose escalation]	Heart Rate	From first dose until the end of Cycle 1 (approximately 35 days)
Primary	Pharmacokinetics of SPYK04 [Dose escalation]	Plasma concentrations of SPYK04	From Cycle 0 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion)
Primary	Pharmacokinetics of SPYK04 [Dose escalation]	Maximum plasma concentration (Cmax) of SPYK04	From Cycle 0 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion)
Primary	Pharmacokinetics of SPYK04 [Dose escalation]	Time to reach maximum plasma drug concentration (Tmax) of SPYK04	From Cycle 0 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion)
Primary	Pharmacokinetics of SPYK04 [Dose escalation]	Area under the concentration versus time curve (AUC) of SPYK04	From Cycle 0 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion)
Primary	Preliminary anti-tumor activity of SPYK04 [Cohort expansion]	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)	From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to 42 months (study completion)
Secondary	Preliminary anti-tumor activity of SPYK04 [Dose escalation]	Objective Response	From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to 42 months (study completion)
Secondary	Safety and tolerability of SPYK04 (AEs) [Cohort expansion]	Incidence, nature, and severity of AEs assessed by the NCI CTCAE v5.0	From Cycle 1 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion)
Secondary	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	From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to 42 months (study completion)
Secondary	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	From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to 42 months (study completion)
Secondary	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	From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to 42 months (study completion)
Secondary	Pharmacokinetics of SPYK04 [Cohort expansion]	Plasma concentrations of SPYK04	From Cycle 1 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion)
Secondary	Pharmacokinetics of SPYK04 [Cohort expansion]	Maximum plasma concentration (Cmax) of SPYK04	From Cycle 1 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion)
Secondary	Pharmacokinetics of SPYK04 [Cohort expansion]	Time to reach maximum plasma drug concentration (Tmax) of SPYK04	From Cycle 1 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion)
Secondary	Pharmacokinetics of SPYK04 [Cohort expansion]	Area under the concentration versus time curve (AUC) of SPYK04	From Cycle 1 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion)
Secondary	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)	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