Summary
This is a Phase 1 study to assess safety, tolerability, pharmacokinetics, immunogenicity, and antitumor activity of ARR-002 in advanced or metastatic ovarian or endometrial cancer.
Detailed Description
This is an open-label, multicenter Phase 1a/1b dose-escalation/expansion, consecutive-cohort, to assess safety, tolerability, pharmacokinetics, immunogenicity, and preliminary antitumor activity of ARR-002 in adults with locally advanced or metastatic ovarian or endometrial cancer.
The study will consist of 2 main parts:
* Phase 1a will enroll participants with platinum-resistant ovarian cancer (PROC). This dose-escalation portion will assess the safety and tolerability of ARR-002.
* Phase 1b will enroll cohorts of participants by cancer type; platinum-resistant ovarian cancer (PROC) and endometrial cancer.
Eligibility Criteria
Age Range: 18 years to No maximum
Inclusion Criteria:
* Patients with histologically and cytologically confirmed advanced or metastatic ovarian, primary peritoneal, or fallopian tube cancer, and platinum resistant who have failed or intolerant to standard therapy, or without alternative standard therapy.
* Patients must have at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
* Tumor specimen available for testing, or agree to biopsy at baseline.
* The score of Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Life expectancy ≥ 12 weeks.
* Organ functions and coagulation function must meet the basic requirements.
* Patients with childbearing potential must use effective contraception during the treatment and for 6 months after the last dose of treatment.
Exclusion Criteria:
* Prior treatment with auristatin-derived drugs s (eg, MMAE and monomethyl auristatin F \[MMAF\]).
* Received antitumor therapy within 4 weeks prior to the first dose or 5 half-lives, whichever is shorter.
* Infection of active hepatitis B, active hepatitis C, or HIV.
* Symptomatic Central nervous system and/or meninges metastasis.
* History of uncontrolled diabetes mellitus or diabetic neuropathy within 3 months before the first dose of study treatment.
* Previous drug-induced interstitial lung disease (ILD) or active ILD.
* Poorly controlled pleural, peritoneal, and pelvic effusion, or combined pericardial effusion.
* History of recurrent gastrointestinal (GI) obstruction.
* Patients with more than one cancer.
* Any other diseases, pulmonary dysfunction, metabolic dysfunction, physical examination finding, or clinical laboratory finding
* Grade ≥ 2 peripheral neuropathy
* History of severe cardiovascular diseases.
* Current use of anticoagulants or thrombolytic agents for therapeutic purposes.
* Known allergic reactions to any component of ARR-002.
* Prior treatment with MUC16- or NaPi2b-targeting agents.
* Ocular conditions such as keratitis or corneal ulceration, monocularity, corneal transplantation, uncontrolled retinopathy, wet macular degeneration, uveitis, papilledema, or optic disc disorder.
* Other situations that are not suitable to participate a clinical trial per investigator's judgement.