A Study of CUSP06 in Patients with Platinum-Refractory/Resistant Ovarian Cancer and Other Advanced Solid Tumors

Inclusion Criteria:

• Written informed consent provided prior to any screening procedures.

• Male or female patients, ≥18 years of age at the time of obtaining informed consent.

• Patients with histologically or cytologically confirmed advanced solid tumorspreviously treated with standard of care systemic therapy, or for whom no standardtherapy is available.

• Willingness to provide archival tumor tissue collected within the previous 2 years,when available. If no archival tissue is available that was collected within a 2year timeframe, willingness to undergo a pretreatment biopsy if medically feasibleand safe.

• For patients on Phase 1b dose expansion, willingness to undergo pre- andon-treatment biopsies if medically feasible and safe.

• Measurable disease per RECIST 1.1.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and lifeexpectancy of ≥12 weeks.

• Adequate organ function as defined by:

• Absolute neutrophil count (ANC) ≥1.5 x 109/L (1500/µL), withoutcolony-stimulating factor support for the past 14 days.

• Platelets ≥100.0 x 109/L (100 000/µL).

• Hemoglobin ≥9.0 g/dL (without blood transfusion in 2-week period prior toscreening laboratory tests).

• Creatinine clearance (CrCl) ≥45 mL/min as calculated by the Cockcroft-Gaultmethod.

• Serum total bilirubin ≤ 1.5 x the upper limit of normal (ULN).

• Aspartate aminotransferase (AST) ≤2.5 x ULN; alanine aminotransferase (ALT) ≤ 2.5 x ULN.

• International normalized ratio (INR) ≤ 1.5; activated partial thromboplastintime (aPTT) ≤ 1.5 x ULN.

• Left ventricular ejection fraction (LVEF) ≥50% as per echocardiography (ECHO)or multi-gated acquisition scan (MUGA).

• Q wave to T wave (QT) interval corrected for heart rate (QTc) ≤480 ms (Fridericia's formula).

• Women of child-bearing potential (WCBP), defined as a sexually mature woman who hasnot undergone surgical sterilization or who has not been naturally postmenopausalfor at least 12 consecutive months (i.e., who has had menses any time in thepreceding 12 consecutive months) must agree to use 2 effective contraceptivemethods; examples include oral, parenteral, or implantable hormonal contraceptive,intra-uterine device, barrier contraceptive with spermicide, partner's latex (orpolyisoprene, if latex allergy) condom or vasectomy while on study treatment and forat least 12 weeks after the last dose of the study drug.

• WCBP must have a negative serum pregnancy test within 72 hours prior to firstdose of the study drug.

• Male patients must agree to use a latex (or polyisoprene, if latex allergy)condom, even if they had a successful vasectomy, while on study treatment andfor at least 12 weeks after the last dose of the study drug.

• Patients must be willing and able to sign the informed consent form, and to adhereto the study visit schedule and other protocol requirements.

Exclusion Criteria:

• Prior treatment an ADC with a topoisomerase I (TOP1) payload.

• Active or progressing brain metastases or evidence of leptomeningeal disease.Stable/treated brain metastases are permitted (defined as history of brainmetastases previously treated with surgical resection or stereotactic radiosurgery,stable on baseline screening study MRI brain for at least 2 months (compared tocomparator MRI brain) and asymptomatic without requirement for steroids orantiseizure medications.

• Persistent toxicities from previous systemic antineoplastic treatments of Grade >1,excluding alopecia and vitiligo.

• Systemic antineoplastic therapy within 5 half-lives or 4 weeks, whichever isshorter, prior to first dose of the study drug, including investigational agents.

• Wide-field radiotherapy (e.g., >30% of marrow-bearing bones) within 4 weeks, orfocal radiation with palliative intent outside the field of measurable diseasewithin 2 weeks prior to first dose of the study drug.

• Major surgery (not including placement of vascular access device or tumor biopsies)within 4 weeks prior to first dose of study drug, or no recovery from side effectsof such intervention.

• Has had clinically significant lung disease requiring systemic corticosteroidtreatment within the last 6 months of randomization/registration (e.g., interstitialpneumonia, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis) or whoare suspected to have such diseases by imaging at screening period.

• Patients with acute or chronic pancreatitis and/or any cirrhosis except cirrhosisdiagnosed as Child-Pugh class A.

• Hepatic insufficiency manifesting as clinical jaundice, hepatic encephalopathy,and/or variceal bleed within 60 days prior to study entry.

• History of liver transplant.

• Prior allogeneic bone marrow transplantation.

• Significant cardiac disease, such as recent (within 6 months prior to first dose ofthe study drug) myocardial infarction or acute coronary syndromes (includingunstable angina pectoris), congestive heart failure (New York Heart Associationclass III or IV), uncontrolled hypertension, uncontrolled cardiac arrhythmias,severe aortic stenosis.

• History of thromboembolic or cerebrovascular events, including transient ischemicattacks, cerebrovascular accidents, deep vein thrombosis, or pulmonary emboli within 3 months prior to first dose of the study drug.

• Acute and/or clinically significant bacterial, fungal, or viral infection includinghepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV).

• Note: patients with chronic HBV, HCV or HIV infection will be eligible if theyare considered upon a mutual agreement of the Investigator and the MedicalMonitor as safe for enrollment and meet one of the following additionalconditions:

• Patients with HIV infection are on an established antiretroviral therapy for atleast 4 weeks, and have CD4+ T-cell counts ≥350 cells/µL and HIV viral load <400 copies/mL,

• Patients with serologic evidence of chronic HBV infection receive concurrentanti-HBV therapy and have HBV viral load below the limit of quantification,

• Patients with a history of HCV infection must have completed curative anti-HCVtherapy and have HCV viral load below the limit of quantification,

• Patients on concurrent anti-HCV therapy have HCV viral load below the limit ofquantification.

• Known or suspected allergy to the study drug or any component of the study drug.

• Concurrent participation in another investigational clinical trial.

• Pregnant or breast-feeding females.

• Prior history of malignancy other than inclusion diagnosis within 3 years prior tofirst dose of the study drug.

• Note: patients with adequately treated basal cell or squamous cell skin cancer,non-invasive superficial bladder cancer, in situ cervical cancer, in situbreast cancer, in situ prostate cancer may be eligible if have shown noevidence of active disease for 2 years prior to first dose of drug.

• Any other severe acute or chronic medical or psychiatric conditions or laboratoryabnormality that may increase the risk associated with the study participation orthe study drug administration or may interfere with the interpretation of studyresults and, in the judgment of the Investigator, would make the patientinappropriate for enrollment in this study.