Metastatic or locally advanced unresectable solid tumors in following indications: breast carcinoma, castration-resistant prostate carcinoma, non-small cell lung carcinoma, epithelial ovarian carcinoma, endometrial carcinoma, head and neck squamous cell carcinoma, or cholangiocarcinoma MedDRA version: 20.0 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 100000020935
Conditions
Sponsors
CytomX Therapeutics, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed diagnosis of any active metastatic or locally advanced unresectable solid tumor. Subjects with advanced or metastatic solid tumors who have disease progression after treatment with available therapies that are known to confer clinical benefit, or who are intolerant to treatment in following indications: breast carcinoma, castration-resistant prostate cancer, non-small cell lung cancer (incl adenocarcinoma and squamous cell subtypes), overian carcinoma, endometrial carcinoma, head and neck squamous cell carcinoma, cholangiocarcinoma 2. Agrees to provide tumor tissue, archival, new or recent acquisition confirmed to be available prior to initiation of study drug for performance of correlative tissue and cellular studies from a tumor site not previously irradiated 3. Evaluable or measurable disease for dose escalation part A and measurable disease required for dose expansion cohorts part B 4. Subjects with treated brain metastases are eligible if brain metastases are stable and subject does not require radiation therapy or steroids. Active screening for brain metastases is not required. 5. At least 18 y of age 6. Eastern Cooperative Oncology Group performance status of 0 or 1 7. Anticipated life expectancy of at least 3 months 8. screening lab values must meet following criteria: absolute neutrophil count >=1500µl; platelet count >= 100 x 10³/µl (must not have been transfused within prev. 10 days); hemoglobin >=9.0 g/dL (may have been transfused); serum creatinine =65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1. Neuropathie > grade 1 2. Active chronic corneal disorder, including but not limited to the following: sjogren's syndrome, Fuchs corneal dystropathy (requiring treatment), history of corneal transplantation, active herpetic keratitis, and also active ocular conditions requiring ongoing treatment/monitoring such as wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, presensce of papilledema and acquired monocular vision 3. Serious concurrent illness, including, but not limited to following: - clinically relevant active infection including known active hepatitis B or C. HIV infection or CMV infection or any other known concurrent infectious disease requiring IV antibiotics within 2 weeks of study enrollment - history of or current active autoimmune diseases, including but not limited to inflammatory bowel diseases, RA, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis, systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies or type 1 insuline dependent diabetes mellitus - significant cardiac disease such as recent MI (class II), uncontrolled hypertension (NCI CTCAE v.4.03 grade 3 or higher), uncontrolled cardiac arrythmias, severe aortic stenosis or >= grade 3 cardiac toxicity following prior chemotherapy - History of multiple sclerosis or other demyelinating disease, Eaton-Lambert syndrome (para-neoplastic syndrome), history of hemorrhagic or ischemic stroke within the last 6 months, or alcoholic liver disease - Non-healing wound(s) or ulcer(s) except for ulcerative lesions caused by the underlying neoplasm - Psychiatric illness/social situations that would limit compliance with study requirements - Interstitial lung disease irrespective of etiology 4. Advanced or metastatic Stage IV NSCLC subjects with epidermal growth factor receptor or anaplastic lymphoma kinase genomic alterations unless they have progressed on treatment with appropriate targeted therapy, including osimertinib for T790M mutation-positive NSCLC 5. Any other anti-cancer treatment such as chemotherapy, immunotherapy, biochemotherapy, radiotherapy, investigative therapy, or high-dose steroids within 30 days of receiving study drug. Low-dose steroids, luteinizing hormone-releasing hormone, aromatase inhibitors (eg, anastrozole), at doses that have been stable for 30 days are permitted for subjects with CRPC 6. History of severe allergic or anaphylactic reactions to previous monoclonal antibody therapy 7. Prior treatment with maytansinoid-containing drug conjugates 8. Subjects with a previously documented absence of thiol-S-purine methyltransferase activity 9. Unresolved acute toxicity NCI CTCAE v4.03 Grade >1 (or baseline, whichever is greater) from prior anti-cancer therapy. Alopecia and other non-acute toxicities are acceptable 10. History of malignancy that is active within the previous 2 years except for localized cancers that are not related to the current cancer being treated, are considered to have been cured and in the opinion of the Investigator, present a low risk for recurrence, including basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the prostate, cervix or breast 11. Currently receiving anticoagulation therapy with warfarin 12. The subject has undergone major surgery (requiring general anesthesia)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to determine the safety profile of CX-2009, the maximum tolerated dose (MTD) / Recommended Phase 2 Dose (RP2D), and the dose-limiting toxicities (DLTs) of CX-2009, when administered intravenously (IV) every 21 days as monotherapy to subjects with selected advanced or recurrent solid tumors.;Secondary Objective: Evaluate preliminary efficacy in subjects treated with CX-2009 as monotherapy Characterize the pharmacokinetics (PK) of CX-2009 Assess the incidence of anti-drug antibody (ADA) formation to CX-2009;Primary end point(s): Dose-limiting toxicities Study-drug related AEs and AEs leading to discontinuation Changes from baseline in clinical laboratory results and vital signs;Timepoint(s) of evaluation of this end point: Administrative interim analyses on safety and efficacy or on PK, immunogenicity, and selected biomarkers may be performed at several times prior to completion of the study in order to facilitate program decisions and to support study presentations or publications | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Objective Response Rate (ORR) is the primary efficacy endpoint Duration of response (DOR) Time To Tumor Response (TTR) Progression-free survival (PFS) Overall survival (OS) Characterize the pharmacokinetics (PK) of CX-2009, including the following analytes: o Intact CX-2009 (referring to the prodrug form of CX-2009 ± DM4); o Total CX-2009 (intact and activated forms of CX-2009 ± DM4); o Total CX-2009-conjugated DM4 (antibody conjugated-DM4); o Free DM4; and o S-methyl DM4 (DM4-Me) - a DM4 metabolite with potent cytotoxic activity;Timepoint(s) of evaluation of this end point: Administrative interim analyses on safety and efficacy or on PK, immunogenicity, and selected biomarkers may be performed at several times prior to completion of the study in order to facilitate program decisions and to support study presentations or publications | — |
Countries
Germany, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Team
CytomX Therapeutics, Inc
Outcome results
None listed