Ignite Creation Date:
2024-05-06 @ 2:46 PM
Last Modification Date:
2024-10-26 @ 1:37 PM
Study NCT ID:
NCT04418167
Status:
SUSPENDED
Last Update Posted:
2024-02-02
First Post:
2020-05-11
Brief Title:
JSI-1187-01 Monotherapy and in Combination With Dabrafenib for Advanced Solid Tumors With MAPK Pathway Mutations
Sponsor:
JS InnoPharm LLC
Organization:
JS InnoPharm LLC
Study Overview
Official Title:
A Phase 1 Study of ERK12 Inhibitor JSI-1187 Administered as Monotherapy and in Combination With Dabrafenib for the Treatment of Advanced Solid Tumors With MAPK Pathway Mutations
Status:
SUSPENDED
Status Verified Date:
2023-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Sponsor decision
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a Phase 1 study of JSI-1187 as monotherapy and in combination with dabrafenib for the treatment of advanced solid tumors with MAPK pathway mutations including mutations that cause MAPK pathway hyperactivation
Detailed Description:
Selected subjects will include males and females age 18 years histologically confirmed locally advanced or metastatic solid tumors with archived tumor sample from the primary recurrent or metastatic disease with documented MAPK pathway mutation or pathway hyperactivating mutations advanced or recovered from all acute toxicities Grade 1 due to prior therapy adequate renal and hepatic function and no known history of significant cardiac or retinal disease
Part A Monotherapy Dose Escalation Following screening a total of up to 80 subjects are anticipated to establish the MTD of JSI-1187 monotherapy in subjects with locally advanced or metastatic solid tumors with MAPK pathway mutations including hyperactivating pathway mutations or gene fusions refractory to or relapsed on prior therapy JSI-1187 will be administered orally at doses of 2 4 and 8 mg twice daily and at doses of 16 24 36 56 88 and 128 mg once or twice daily or until an MTD for both regimens is reached whichever is earlier repeated every 28 days 1 cycle A 33 dose escalation schema will be followed to establish the MTD of the JSI-1187 monotherapy Subjects will take their doses in a fasted state 1 hour before or 2 hours after a meal A total of 6 subjects will be treatment at the MTD before starting Part B
On hold effective 05 July 2023 Part B Combination Dose Escalation Following screening a total of up to 36 subjects are anticipated to establish the MTD of JSI-1187 plus dabrafenib in BRAF V600EK-mutated unresectable or metastatic melanoma BRAF V600E-mutated metastatic non-small cell lung cancer NSCLC BRAF V600E-mutated locally advanced or metastatic anaplastic thyroid cancer or other BRAF V600E-mutated unresectable or metastatic solid tumors A 33 dose escalation schema will be followed to establish the MTD of the JSI-1187 plus dabrafenib combination Daily doses of both drugs will be taken in the fasted state A total of 6 subjects will be treated at the JSI-1187 plus dabrafenib combined MTD before beginning Part C
On hold effective 05 July 2023 Part C Expansion Cohorts Following screening a total of 58 subjects in 3 cohorts are anticipated to expand the disease treatment settings of JSI-1187 in combination with dabrafenib in BRAF V600EK-mutated melanoma or BRAF V600E-mutated NSCLC
Cohort 1 JSI-1187 plus dabrafenib in BRAF V600EK-mutated unresectable or metastatic melanoma after 1-3 prior therapies for metastatic disease including anti-PD1 therapy with or without ipilimumab and BRAFMEK inhibitor treatment n21
Cohort 2 JSI-1187 plus dabrafenib in BRAF V600EK-mutated unresectable or metastatic melanoma after BRAFMEK inhibitor adjuvant therapy for Stage 3 disease followed by 1-2 prior therapies for metastatic disease including anti-PD-1 therapy with or without ipilimumab and excluding BRAFMEK inhibitor treatment n21
Cohort 3 JSI-1187 plus dabrafenib in BRAF V600E-mutated metastatic NSCLC after 1-2 prior therapies for metastatic disease n16
JSI-1187 plus dabrafenib will be administered at the MTDs established for both drugs in Part B repeated every 28 days 1 cycle
Subjects who demonstrate clinical benefit CR PR or SD will be allowed to continue therapy with JSI-1187 and dabrafenib until progression of disease observation of unacceptable adverse events intercurrent illness or changes in the subjects condition that prevents further study participation
Disease response will be assessed according to Response Evaluation Criteria in Solid Tumors RECIST v11
Blood for hematology coagulation parameters and serum chemistry determinations will be collected ECGs will be taken and ophthalmologic exams will be conducted during the study
Blood will be collected for PK assessment of JSI-1187 and PD assessment of pRSKRSK ratio determinations
Tumor biopsies optional will be collected from consenting subjects at Screening and on-study for pRSK determination Results will be correlated with clinical outcome
Part A Monotherapy Dose Escalation Following screening a total of up to 80 subjects are anticipated to establish the MTD of JSI-1187 monotherapy in subjects with locally advanced or metastatic solid tumors with MAPK pathway mutations including hyperactivating pathway mutations or gene fusions refractory to or relapsed on prior therapy JSI-1187 will be administered orally at doses of 2 4 and 8 mg twice daily and at doses of 16 24 36 56 88 and 128 mg once or twice daily or until an MTD for both regimens is reached whichever is earlier repeated every 28 days 1 cycle A 33 dose escalation schema will be followed to establish the MTD of the JSI-1187 monotherapy Subjects will take their doses in a fasted state 1 hour before or 2 hours after a meal A total of 6 subjects will be treatment at the MTD before starting Part B
On hold effective 05 July 2023 Part B Combination Dose Escalation Following screening a total of up to 36 subjects are anticipated to establish the MTD of JSI-1187 plus dabrafenib in BRAF V600EK-mutated unresectable or metastatic melanoma BRAF V600E-mutated metastatic non-small cell lung cancer NSCLC BRAF V600E-mutated locally advanced or metastatic anaplastic thyroid cancer or other BRAF V600E-mutated unresectable or metastatic solid tumors A 33 dose escalation schema will be followed to establish the MTD of the JSI-1187 plus dabrafenib combination Daily doses of both drugs will be taken in the fasted state A total of 6 subjects will be treated at the JSI-1187 plus dabrafenib combined MTD before beginning Part C
On hold effective 05 July 2023 Part C Expansion Cohorts Following screening a total of 58 subjects in 3 cohorts are anticipated to expand the disease treatment settings of JSI-1187 in combination with dabrafenib in BRAF V600EK-mutated melanoma or BRAF V600E-mutated NSCLC
Cohort 1 JSI-1187 plus dabrafenib in BRAF V600EK-mutated unresectable or metastatic melanoma after 1-3 prior therapies for metastatic disease including anti-PD1 therapy with or without ipilimumab and BRAFMEK inhibitor treatment n21
Cohort 2 JSI-1187 plus dabrafenib in BRAF V600EK-mutated unresectable or metastatic melanoma after BRAFMEK inhibitor adjuvant therapy for Stage 3 disease followed by 1-2 prior therapies for metastatic disease including anti-PD-1 therapy with or without ipilimumab and excluding BRAFMEK inhibitor treatment n21
Cohort 3 JSI-1187 plus dabrafenib in BRAF V600E-mutated metastatic NSCLC after 1-2 prior therapies for metastatic disease n16
JSI-1187 plus dabrafenib will be administered at the MTDs established for both drugs in Part B repeated every 28 days 1 cycle
Subjects who demonstrate clinical benefit CR PR or SD will be allowed to continue therapy with JSI-1187 and dabrafenib until progression of disease observation of unacceptable adverse events intercurrent illness or changes in the subjects condition that prevents further study participation
Disease response will be assessed according to Response Evaluation Criteria in Solid Tumors RECIST v11
Blood for hematology coagulation parameters and serum chemistry determinations will be collected ECGs will be taken and ophthalmologic exams will be conducted during the study
Blood will be collected for PK assessment of JSI-1187 and PD assessment of pRSKRSK ratio determinations
Tumor biopsies optional will be collected from consenting subjects at Screening and on-study for pRSK determination Results will be correlated with clinical outcome
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None