A Study to Evaluate INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms
A Study to Evaluate INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms
This study is being conducted to evaluate the safety, tolerability, dose-limiting toxicity (DLT) and determine the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion (RDE) of INCA033989 administered as a Monotherapy or in Combination With Ruxolitinib in participants with myeloproliferative neoplasms.
Leukemia
Phase I
Adults
Mol. targeted/Immunotherapy/Biologics
INCA033989,
Ruxolitinib
Mohan, Sanjay
National
Vanderbilt University
03-18-2024
Eligibility
18 Years and older
ALL
false
Inclusion Criteria:
Life expectancy > 6 months.
Life expectancy > 6 months.
Willingness to undergo a pretreatment and regular on-study BM biopsies and aspirates (as appropriate to disease).
Willingness to undergo a pretreatment and regular on-study BM biopsies and aspirates (as appropriate to disease).
Existing documentation from a qualified local laboratory of CALR exon-9 mutation.
Existing documentation from a qualified local laboratory of CALR exon-9 mutation.
Participants with MF or ET as defined in the protocol.
Participants with MF or ET as defined in the protocol.
Exclusion Criteria:
Presence of any hematological malignancy other than ET, PMF, or post-ET MF.
Presence of any hematological malignancy other than ET, PMF, or post-ET MF.
Prior history of major bleeding, or thrombosis within the last 3 months prior to study enrollment.
Prior history of major bleeding, or thrombosis within the last 3 months prior to study enrollment.
Participants with laboratory values exceeding the protocol defined thresholds.
Participants with laboratory values exceeding the protocol defined thresholds.
Has undergone any prior allogenic or autologous stem-cell transplantation or such transplantation is planned.
Has undergone any prior allogenic or autologous stem-cell transplantation or such transplantation is planned.
Active invasive malignancy over the previous 2 years.
Active invasive malignancy over the previous 2 years.
History of clinically significant or uncontrolled cardiac disease.
History of clinically significant or uncontrolled cardiac disease.
Active HBV/HCV or known history of HIV.
Active HBV/HCV or known history of HIV.
Any prior chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, biological therapy, endocrine therapy, targeted therapy, antibody, or hypomethylating agent used to treat the participant's disease, with the exception of ruxolitinib for TGBs only, within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.
Any prior chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, biological therapy, endocrine therapy, targeted therapy, antibody, or hypomethylating agent used to treat the participant's disease, with the exception of ruxolitinib for TGBs only, within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.
Participants undergoing treatment with G-CSF, GM-CSF, or TPO-R agonists at any time within 4 weeks before the first dose of study treatment.
Participants undergoing treatment with G-CSF, GM-CSF, or TPO-R agonists at any time within 4 weeks before the first dose of study treatment.
Other protocol-defined Inclusion/Exclusion Criteria may apply.
Other protocol-defined Inclusion/Exclusion Criteria may apply.
Life expectancy > 6 months.
Life expectancy > 6 months.
Willingness to undergo a pretreatment and regular on-study BM biopsies and aspirates (as appropriate to disease).
Willingness to undergo a pretreatment and regular on-study BM biopsies and aspirates (as appropriate to disease).
Existing documentation from a qualified local laboratory of CALR exon-9 mutation.
Existing documentation from a qualified local laboratory of CALR exon-9 mutation.
Participants with MF or ET as defined in the protocol.
Participants with MF or ET as defined in the protocol.
Exclusion Criteria:
Presence of any hematological malignancy other than ET, PMF, or post-ET MF.
Presence of any hematological malignancy other than ET, PMF, or post-ET MF.
Prior history of major bleeding, or thrombosis within the last 3 months prior to study enrollment.
Prior history of major bleeding, or thrombosis within the last 3 months prior to study enrollment.
Participants with laboratory values exceeding the protocol defined thresholds.
Participants with laboratory values exceeding the protocol defined thresholds.
Has undergone any prior allogenic or autologous stem-cell transplantation or such transplantation is planned.
Has undergone any prior allogenic or autologous stem-cell transplantation or such transplantation is planned.
Active invasive malignancy over the previous 2 years.
Active invasive malignancy over the previous 2 years.
History of clinically significant or uncontrolled cardiac disease.
History of clinically significant or uncontrolled cardiac disease.
Active HBV/HCV or known history of HIV.
Active HBV/HCV or known history of HIV.
Any prior chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, biological therapy, endocrine therapy, targeted therapy, antibody, or hypomethylating agent used to treat the participant's disease, with the exception of ruxolitinib for TGBs only, within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.
Any prior chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, biological therapy, endocrine therapy, targeted therapy, antibody, or hypomethylating agent used to treat the participant's disease, with the exception of ruxolitinib for TGBs only, within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.
Participants undergoing treatment with G-CSF, GM-CSF, or TPO-R agonists at any time within 4 weeks before the first dose of study treatment.
Participants undergoing treatment with G-CSF, GM-CSF, or TPO-R agonists at any time within 4 weeks before the first dose of study treatment.
Other protocol-defined Inclusion/Exclusion Criteria may apply.
Other protocol-defined Inclusion/Exclusion Criteria may apply.
