A Dose-Escalation Study of SPYK04 in Patients With Locally Advanced or Metastatic Solid Tumors (With Expansion).
- Conditions
- Locally Advanced or Metastatic Solid Tumors
- Interventions
- Registration Number
- NCT04511845
- Lead Sponsor
- Chugai Pharmaceutical
- Brief Summary
Phase I, open-label, multi-center study
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 113
(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)
(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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dose escalation cohort of SPYK04 SPYK04 Patients will receive SPYK04 at escalated dose. Expansion part in NSCLC, ovarian cancer and other solid tumors SPYK04 Patients will receive SPYK04 at the recommended dose.
- Primary Outcome Measures
Name Time Method 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 (Electrocardiograms in triplicate) [Dose escalation] From first dose until the end of Cycle 1 (approximately 35 days) Heart Rate
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)
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
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) Area under the concentration versus time curve (AUC) of SPYK04
- Secondary Outcome Measures
Name Time Method 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 [Dose escalation] From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to 42 months (study completion) Objective Response
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) 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
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) Area under the concentration versus time curve (AUC) 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)
Trial Locations
- Locations (15)
Kurume University Hospital
🇯🇵Kurume, Fukuoka, Japan
National Hospital Organization Kyushu Cancer Center
🇯🇵Fukuoka, Japan
Arizona Oncology
🇺🇸Tucson, Arizona, United States
National Cancer Center Hospital
🇯🇵Chuo Ku, Tokyo, Japan
Osaka Prefectural Hospital Organization Osaka International Cancer Center
🇯🇵Osaka, Japan
Rocky Mountain Cancer Centers
🇺🇸Lone Tree, Colorado, United States
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
Cancer Institute Hospital of Japanese Foundation for Cancer Research
🇯🇵Koto-Ku, Tokyo, Japan
Texas Oncology
🇺🇸Tyler, Texas, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Froedtert Hospital and the Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Minnesota Oncology
🇺🇸Minneapolis, Minnesota, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States