A Phase 1, First-in-Human Study of CUSP06, a Cadherin-6 (CDH6)-directed Antibody-Drug Conjugate, in Patients with Platinum-Refractory/Resistant Ovarian Cancer and Other Advanced Solid Tumors

This phase 1 study will evaluate the safety, tolerability, pharmacokinetics, and efficacy
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 tumors
previously treated with standard of care systemic therapy, or for whom no standard
therapy is available.

- Willingness to provide archival tumor tissue, when available. If no archival tissue
is available, willingness to undergo a pretreatment biopsy if medically feasible and
safe.

- Measurable disease per RECIST v1.1.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and life
expectancy of ≥12 weeks.

- Adequate organ function as defined by:

- Absolute neutrophil count (ANC) ≥1.5 x 109/L (1500/µL), without
colony-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 to
screening).

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

- 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 thromboplastin
time (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 has
not undergone surgical sterilization or who has not been naturally postmenopausal
for at least 12 consecutive months must agree to use a highly effective
contraceptive method

- Patients must be willing and able to sign the informed consent form, and to adhere
to 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 brain
metastases previously treated with surgical resection or stereotactic radiosurgery,
stable on baseline screening study MRI brain for at least 2 months (compared to
comparator MRI brain) and asymptomatic without requirement for steroids or
antiseizure 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, including
investigational agents.

- Wide-field radiotherapy (e.g., >30% of marrow-bearing bones) within 4 weeks, or
focal radiation with palliative intent outside the field of measurable disease
within 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 from
side effects of such intervention.

- Has had clinically significant lung disease requiring systemic corticosteroid
treatment within the last 6 months of randomization/registration (e.g., interstitial
pneumonia, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis) or who
are suspected to have such diseases by imaging at screening period.

- Patients with acute or chronic pancreatitis and/or liver cirrhosis except well
compensated 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 of
the study drug) myocardial infarction or acute coronary syndromes (including
unstable angina pectoris), congestive heart failure (New York Heart Association
class III or IV), uncontrolled hypertension, uncontrolled cardiac arrhythmias,
severe aortic stenosis.

- History of thromboembolic or cerebrovascular events, including transient ischemic
attacks, 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 including
hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV).

- Note: patients with chronic HBV, HCV or HIV infection will be eligible if they
are considered upon a mutual agreement of the Investigator and the Medical
Monitor as safe for enrollment and meet one of the following additional
conditions:

- Patients with HIV infection are on an established antiretroviral therapy for at
least 4 weeks, and have CD4+ T-cell counts ≥350 cells/µL and HIV viral load <50
copies/mL,

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

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

- Patients on concurrent anti-HCV therapy have HCV viral load below the limit of
quantification.

- 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 to
first dose of the study drug.

- Note: excluding patients with adequately treated basal cell or squamous cell
skin cancer, non-invasive superficial bladder cancer, in situ cervical cancer,
in situ breast cancer, and in situ prostate cancer. Other malignancies with low
risk of recurrence may also be considered following discussion with the Medical
Monitor.

- Any other severe acute or chronic medical or psychiatric conditions or laboratory
abnormality that may increase the risk associated with the study participation or
the study drug administration or may interfere with the interpretation of study
results and, in the judgment of the Investigator, would make the patient
inappropriate for enrollment in this study.

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

- Gastrointestinal obstruction or radiographic evidence of gastrointestinal
obstruction 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 days
prior to first dose of study drug or inability to discontinue use of a strong CYP3A4
or CYP1A2 inducer or inhibitor for the duration of the study.

- Ascites requiring frequent paracentesis for symptomatic management.