Open-Label Study of the CDK4/6 Inhibitor SPH4336 in Subjects With Locally Advanced or Metastatic Liposarcomas
Open-Label Study of the CDK4/6 Inhibitor SPH4336 in Subjects With Locally Advanced or Metastatic Liposarcomas
Study SPH4336-US-01 is an open-label (no placebo), multicenter clinical trial to evaluate the
safety, blood levels (pharmacokinetics) and preliminary anti-tumor effects of SPH4336, a
selective enzyme blocker, in patients with specific types of liposarcomas (tumors expressing
the target of the study drug).
safety, blood levels (pharmacokinetics) and preliminary anti-tumor effects of SPH4336, a
selective enzyme blocker, in patients with specific types of liposarcomas (tumors expressing
the target of the study drug).
Sarcoma
Phase II
Adults
Mol. targeted/Immunotherapy/Biologics
SPH4336
Keedy, Vicki
National
Vanderbilt University
04-16-2024
Eligibility
18 Years
BOTH
NO
Inclusion Criteria:
Informed consent
18 years of age
ECOG performance status 0 or 1
Histologically confirmed, locally advanced or metastatic sarcoma
Dedifferentiated or well-differentiated/dedifferentiated liposarcomas
No more than 3 prior lines of treatment
Evidence of progression as evidenced by at least one of the following within the past 3 months:
An increase of at least 20% in measurable tumors
The appearance of new lesions
Unequivocal progression of non-measurable lesions
Measurable disease per RECIST v1.1
If residual treatment-related toxicity from prior therapy:
All treatment-related toxicity resolved to Grade 1 or baseline (alopecia excepted)
ANC 1,500/L
Platelets 100,000/L
Hgb 9.0 g/dL (in the absence of pRBC transfusion over the prior 4 weeks)
Estimated glomerular filtration rate of 60 mL/min (based on the Cockcroft and Gault formula for individualized estimates of GFR)
Total bilirubin 1.5 x the Upper Limit of Normal (ULN) or 3 x ULN if known Gilbert's disease
AST and ALT 3 x ULN or 5 x ULN if malignant involvement of the liver
Sterile or willing to use effective contraception (approved hormonal contraceptive such as oral contraceptives, patches, implants, injections, rings or hormonally-impregnated intrauterine device (IUD), or an IUD in women of childbearing potential and a condom in men) during the study and for 3 months following the last dose of study drug
Availability of archived tumor tissue or willingness to undergo a baseline tumor biopsy, and in the first 10 study subjects, to determine baseline tumor biomarker levels and a willingness to undergo a second tumor biopsy at C1D15 to assess treatment-induced changes in tumor biomarker levels
Exclusion Criteria:
Prior treatment with a CDK4/6-targeted agent
Patient's tumor known to be CDK4 negative
Anticancer therapy (e.g., chemotherapy, biologics, irradiation) within 14 days or 5 half-lives (whichever is greater) of screening
Major surgery within 28 days of screening
Requirement for systemic treatment with strong CYP3A4 inhibitors or inducers of CYP3A4 at study entry
Central nervous system metastases or leptomeningeal disease, unless appropriately treated and neurologically stable without steroids for 28 days
Other malignancy unless disease-free for 2 years and not expected to relapse or require treatment during study participation
Active systemic infection or severe localized infection
Known HIV-positive with CD4+ cell counts 350 cells/uL or a history of an AIDS-defining opportunistic infection
Known hepatitis B virus (HBV) or hepatitis C virus (HCV) infection with viral load above the limit of quantification
Active COVID-19 infection
Major cardiac abnormalities (e.g., uncontrolled angina, unstable arrhythmias, myocardial infarction, NYHA Class 3 CHF) 6 months of C1D1
Persistent (3 ECGs 5 mins apart) prolongation of the QTcF (Fridericia) > 470 msec
[Females] Pregnant or nursing
Any other medical or psychiatric condition, or laboratory abnormality that would result in an unacceptable risk with study participation
Presence of active gastrointestinal disease or other condition expected to interfere significantly with absorption, distribution, metabolism or excretion of oral therapy (e.g., ulcerative disease, uncontrolled nausea, vomiting, chronic diarrhea, malabsorption syndrome)
Informed consent
18 years of age
ECOG performance status 0 or 1
Histologically confirmed, locally advanced or metastatic sarcoma
Dedifferentiated or well-differentiated/dedifferentiated liposarcomas
No more than 3 prior lines of treatment
Evidence of progression as evidenced by at least one of the following within the past 3 months:
An increase of at least 20% in measurable tumors
The appearance of new lesions
Unequivocal progression of non-measurable lesions
Measurable disease per RECIST v1.1
If residual treatment-related toxicity from prior therapy:
All treatment-related toxicity resolved to Grade 1 or baseline (alopecia excepted)
ANC 1,500/L
Platelets 100,000/L
Hgb 9.0 g/dL (in the absence of pRBC transfusion over the prior 4 weeks)
Estimated glomerular filtration rate of 60 mL/min (based on the Cockcroft and Gault formula for individualized estimates of GFR)
Total bilirubin 1.5 x the Upper Limit of Normal (ULN) or 3 x ULN if known Gilbert's disease
AST and ALT 3 x ULN or 5 x ULN if malignant involvement of the liver
Sterile or willing to use effective contraception (approved hormonal contraceptive such as oral contraceptives, patches, implants, injections, rings or hormonally-impregnated intrauterine device (IUD), or an IUD in women of childbearing potential and a condom in men) during the study and for 3 months following the last dose of study drug
Availability of archived tumor tissue or willingness to undergo a baseline tumor biopsy, and in the first 10 study subjects, to determine baseline tumor biomarker levels and a willingness to undergo a second tumor biopsy at C1D15 to assess treatment-induced changes in tumor biomarker levels
Exclusion Criteria:
Prior treatment with a CDK4/6-targeted agent
Patient's tumor known to be CDK4 negative
Anticancer therapy (e.g., chemotherapy, biologics, irradiation) within 14 days or 5 half-lives (whichever is greater) of screening
Major surgery within 28 days of screening
Requirement for systemic treatment with strong CYP3A4 inhibitors or inducers of CYP3A4 at study entry
Central nervous system metastases or leptomeningeal disease, unless appropriately treated and neurologically stable without steroids for 28 days
Other malignancy unless disease-free for 2 years and not expected to relapse or require treatment during study participation
Active systemic infection or severe localized infection
Known HIV-positive with CD4+ cell counts 350 cells/uL or a history of an AIDS-defining opportunistic infection
Known hepatitis B virus (HBV) or hepatitis C virus (HCV) infection with viral load above the limit of quantification
Active COVID-19 infection
Major cardiac abnormalities (e.g., uncontrolled angina, unstable arrhythmias, myocardial infarction, NYHA Class 3 CHF) 6 months of C1D1
Persistent (3 ECGs 5 mins apart) prolongation of the QTcF (Fridericia) > 470 msec
[Females] Pregnant or nursing
Any other medical or psychiatric condition, or laboratory abnormality that would result in an unacceptable risk with study participation
Presence of active gastrointestinal disease or other condition expected to interfere significantly with absorption, distribution, metabolism or excretion of oral therapy (e.g., ulcerative disease, uncontrolled nausea, vomiting, chronic diarrhea, malabsorption syndrome)
