Open-Label Study of the CDK4/6 Inhibitor SPH4336 in Subjects With Locally Advanced or Metastatic Liposarcomas

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 thepast 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 (alopeciaexcepted)

• ANC ≥ 1,500/μL

• Platelets ≥ 100,000/μL

• 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 andGault formula for individualized estimates of GFR)

• Total bilirubin ≤ 1.5 x the Upper Limit of Normal (ULN) or ≤ 3 x ULN if knownGilbert'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 contraceptivesuch as oral contraceptives, patches, implants, injections, rings orhormonally-impregnated intrauterine device (IUD), or an IUD in women of childbearingpotential and a condom in men) during the study and for 3 months following the lastdose of study drug

• Availability of archived tumor tissue or willingness to undergo a baseline tumorbiopsy, and in the first 10 study subjects, to determine baseline tumor biomarkerlevels and a willingness to undergo a second tumor biopsy at C1D15 to assesstreatment-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 5half-lives (whichever is greater) of screening

• Major surgery within 28 days of screening

• Requirement for systemic treatment with strong CYP3A4 inhibitors or inducers ofCYP3A4 at study entry

• Central nervous system metastases or leptomeningeal disease, unless appropriatelytreated and neurologically stable without steroids for ≥ 28 days

• Other malignancy unless disease-free for ≥ 2 years and not expected to relapse orrequire 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 anAIDS-defining opportunistic infection

• Known hepatitis B virus (HBV) or hepatitis C virus (HCV) infection with viral loadabove 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 wouldresult in an unacceptable risk with study participation

• Presence of active gastrointestinal disease or other condition expected to interferesignificantly with absorption, distribution, metabolism or excretion of oral therapy (e.g., ulcerative disease, uncontrolled nausea, vomiting, chronic diarrhea,malabsorption syndrome)