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, when available. If no archival tissueis available, willingness to undergo a pretreatment biopsy if medically feasible andsafe.

• Measurable disease per RECIST v1.1.

• 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).

• 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).

• Baseline oxygen saturation on room air ≥ 92%

• Albumin ≥ 3.0 g/dL

• Women of child-bearing potential (WOCBP), defined as a sexually mature woman who hasnot undergone surgical sterilization or who has not been naturally postmenopausalfor at least 12 consecutive months must agree to use a highly effectivecontraceptive method

• 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 with 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 or prohibited co-medications within 5 half-lives or 4 weeks, whichever is shorter, prior to first dose of the study drug, includinginvestigational 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 within 4 weeks prior to first dose of study drug, or no recovery fromside effects of 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 liver cirrhosis except wellcompensated cirrhosis (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 <50copies/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: excluding patients with adequately treated basal cell or squamous cellskin cancer, non-invasive superficial bladder cancer, in situ cervical cancer,in situ breast cancer, and in situ prostate cancer. Other malignancies with lowrisk of recurrence may also be considered following discussion with the MedicalMonitor.

• 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.

• Chest irradiation within 1 year prior to first dose of study drug.

• Gastrointestinal obstruction or radiographic evidence of gastrointestinalobstruction within 4 weeks prior to the first dose of study drug.

• Vaccination with a live vaccine ≤30 days prior to first dose of study drug.

• Use of a strong cytochrome P450 (CYP)3A4 or CYP1A2 inducer or inhibitor ≤14 daysprior to first dose of study drug or inability to discontinue use of a strong CYP3A4or CYP1A2 inducer or inhibitor for the duration of the study.

• Ascites requiring frequent paracentesis for symptomatic management.