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

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

Phase I, open-label, multi-center study

Study Overview

• Status: Active, not recruiting
• Conditions: Locally Advanced or Metastatic Solid Tumors
• Intervention / Treatment: Drug: SPYK04

• Study Type: Interventional
• Enrollment (Estimated): 113
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 811-1395
    • National Hospital Organization Kyushu Cancer Center
  • Osaka, Japan, 541-8567
    • Osaka Prefectural Hospital Organization Osaka International Cancer Center
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Fukuoka
    • Kurume, Fukuoka, Japan, 830-0011
      • Kurume University Hospital
  • Tokyo
    • Chuo Ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
    • Koto-Ku, Tokyo, Japan, 135-8550
      • Cancer Institute Hospital of Japanese Foundation for Cancer Research
• United States
  • Arizona
    • Tucson, Arizona, United States, 85711
      • Arizona Oncology
  • Colorado
    • Lone Tree, Colorado, United States, 80124
      • Rocky Mountain Cancer Centers
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Minnesota Oncology
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
    • Tyler, Texas, United States, 75702
      • Texas Oncology
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital and the Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation cohort of SPYK04; Patients will receive SPYK04 at escalated dose.	Drug: SPYK04; SPYK04 capsule
Experimental: Expansion part in NSCLC, ovarian cancer and other solid tumors; Patients will receive SPYK04 at the recommended dose.	Drug: SPYK04; SPYK04 capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
Safety and tolerability of SPYK04 (Electrocardiograms in triplicate) [Dose escalation]	Heart Rate	From first dose until the end of Cycle 1 (approximately 35 days)
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)
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)
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)
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)
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)
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)
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)
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)
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)
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)
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

Collaborators and Investigators

• Sponsor: Chugai Pharmaceutical
• Investigators: Study Director: Sponsor Chugai Pharmaceutical Co. Ltd, clinical-trials@chugai-pharm.co.jp

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2020
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: July 8, 2020
• First Submitted That Met QC Criteria: August 11, 2020
• First Posted (Actual): August 13, 2020

Study Record Updates

• Last Update Posted (Actual): July 14, 2025
• Last Update Submitted That Met QC Criteria: July 10, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: SPK101JG

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform. For further details on Chugai's Data Sharing Policy and how to request access to related clinical study documents, see here (www.chugai-pharm.co.jp/english/profile/rd/ctds_request.html).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No