Description:
Phase I, open-label, multi-center study
Title
- Brief Title: A Dose-Escalation Study of SPYK04 in Patients With Locally Advanced or Metastatic Solid Tumors (With Expansion).
- 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 IDs
- ORG STUDY ID:
SPK101JG
- NCT ID:
NCT04511845
Conditions
- Locally Advanced or Metastatic Solid Tumors
Interventions
| Drug | Synonyms | Arms |
|---|
| SPYK04 | | Dose escalation cohort of SPYK04 |
Purpose
Phase I, open-label, multi-center study
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Dose escalation cohort of SPYK04 | Experimental | Patients will receive SPYK04 at escalated dose. | |
| Expansion part in NSCLC, ovarian cancer and other solid tumors | Experimental | Patients will receive SPYK04 at the recommended dose. | |
Eligibility Criteria
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)
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Safety and tolerability of SPYK04 (Dose limiting toxicities) [Dose escalation] |
| Time Frame: | From first dose until the end of Cycle 1 (approximately 35 days) |
| Safety Issue: | |
| Description: | Incidence and nature of DLTs |
Secondary Outcome Measures
| Measure: | Preliminary anti-tumor activity of SPYK04 [Dose escalation] |
| Time Frame: | From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to 42 months (study completion) |
| Safety Issue: | |
| Description: | Objective Response |
| Measure: | Safety and tolerability of SPYK04 (AEs) [Cohort expansion] |
| Time Frame: | From Cycle 1 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion) |
| Safety Issue: | |
| Description: | Incidence, nature, and severity of AEs assessed by the NCI CTCAE v5.0 |
| Measure: | Preliminary anti-tumor activity of SPYK04 [Cohort expansion] |
| Time Frame: | From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to 42 months (study completion) |
| Safety Issue: | |
| Description: | 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 |
| Measure: | Preliminary anti-tumor activity of SPYK04 [Cohort expansion] |
| Time Frame: | From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to 42 months (study completion) |
| Safety Issue: | |
| Description: | 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 |
| Measure: | Preliminary anti-tumor activity of SPYK04 [Cohort expansion] |
| Time Frame: | From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first, assessed up to 42 months (study completion) |
| Safety Issue: | |
| Description: | 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 |
| Measure: | Pharmacokinetics of SPYK04 [Cohort expansion] |
| Time Frame: | From Cycle 1 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion) |
| Safety Issue: | |
| Description: | Plasma concentrations of SPYK04 |
| Measure: | Pharmacokinetics of SPYK04 [Cohort expansion] |
| Time Frame: | From Cycle 1 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion) |
| Safety Issue: | |
| Description: | Maximum plasma concentration (Cmax) of SPYK04 |
| Measure: | Pharmacokinetics of SPYK04 [Cohort expansion] |
| Time Frame: | From Cycle 1 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion) |
| Safety Issue: | |
| Description: | Time to reach maximum plasma drug concentration (Tmax) of SPYK04 |
| Measure: | Pharmacokinetics of SPYK04 [Cohort expansion] |
| Time Frame: | From Cycle 1 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion) |
| Safety Issue: | |
| Description: | Area under the concentration versus time curve (AUC) of SPYK04 |
| Measure: | Pharmacodynamics of SPYK04 [Cohort expansion] |
| 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 |
| Safety Issue: | |
| Description: | Expression level of pMEK and pERK in solid tumor tissues (e.g., baseline archival or biopsy, and on treatment biopsy) |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Chugai Pharmaceutical |
Last Updated
February 15, 2021
