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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04511845
Recruitment Status : Not yet recruiting
First Posted : August 13, 2020
Last Update Posted : August 13, 2020
Sponsor:
Information provided by (Responsible Party):
Chugai Pharmaceutical

Brief Summary:
Phase I, open-label, multi-center study

Condition or disease Intervention/treatment Phase
Locally Advanced or Metastatic Solid Tumors Drug: SPYK04 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : August 14, 2020
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : March 31, 2024

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




Primary Outcome Measures :
  1. Safety and tolerability of SPYK04 (Dose limiting toxicities) [Dose escalation] [ Time Frame: From first dose until the end of Cycle 1 (approximately 35 days) ]
    Incidence and nature of DLTs

  2. Safety and tolerability of SPYK04 (Adverse Events) [Dose escalation] [ Time Frame: 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

  3. Safety and tolerability of SPYK04 (Electrocardiograms in triplicate) [Dose escalation] [ Time Frame: From first dose until the end of Cycle 1 (approximately 35 days) ]
    Uncorrected QT interval, QTcF, PR duration, QRS interval and RR interval

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

  5. Pharmacokinetics of SPYK04 [Dose escalation] [ Time Frame: From Cycle 0 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion) ]
    Plasma concentrations of SPYK04

  6. Pharmacokinetics of SPYK04 [Dose escalation] [ Time Frame: From Cycle 0 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion) ]
    Maximum plasma concentration (Cmax) of SPYK04

  7. Pharmacokinetics of SPYK04 [Dose escalation] [ Time Frame: From Cycle 0 Day 1 until 28 days after the last dose of study treatment, assessed up to 42 months (study completion) ]
    Time to reach maximum plasma drug concentration (Tmax) of SPYK04

  8. Pharmacokinetics of SPYK04 [Dose escalation] [ Time Frame: 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

  9. 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) ]
    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)


Secondary Outcome Measures :
  1. 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) ]
    Objective Response

  2. 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) ]
    Incidence, nature, and severity of AEs assessed by the NCI CTCAE v5.0

  3. 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) ]
    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

  4. 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) ]
    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

  5. 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) ]
    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

  6. 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) ]
    Plasma concentrations of SPYK04

  7. 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) ]
    Maximum plasma concentration (Cmax) of SPYK04

  8. 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) ]
    Time to reach maximum plasma drug concentration (Tmax) of SPYK04

  9. 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) ]
    Area under the concentration versus time curve (AUC) of SPYK04

  10. 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 ]
    Expression level of pMEK and pERK in solid tumor tissues (e.g., baseline archival or biopsy, and on treatment biopsy)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04511845


Contacts
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Contact: Clinical trials information only use Email clinical-trials@chugai-pharm.co.jp

Sponsors and Collaborators
Chugai Pharmaceutical
Investigators
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Study Director: Sponsor Chugai Pharmaceutical Co. Ltd clinical-trials@chugai-pharm.co.jp
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Responsible Party: Chugai Pharmaceutical
ClinicalTrials.gov Identifier: NCT04511845    
Other Study ID Numbers: SPK101JG
First Posted: August 13, 2020    Key Record Dates
Last Update Posted: August 13, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). 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).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms