Metastatic or locally advanced unresectable solid tumors in following indications: breast cancer (BC), castrate-resistant prostate carcinoma (CRPC), non-small cell lung carcinoma (NSCLC), ovarian epithelial cancer (EOC), endometrial carcinoma (EC), head and neck squamous cell carcinoma (HNSCC), or cholangiocellular carcinoma (CCC) MedDRA version: 21.1 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 100000004864
Conditions
Sponsors
CytomX Therapeutics, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed diagnosis of active metastatic or locally advanced unresectable solid tumor in subjects 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: Eligible indications, by Part: Part A: BC, CRPC, NSCLC (including adenocarcinoma and squamous cell subtypes), OEC, EC, HNSCC, and CCC; Part A2: BC, NSCLC (including adenocarcinoma and squamous cell subtypes), OEC,EC, and HNSCC; Parts B, C2, and D2: TNBC, hormone receptor (HR; ie, estrogen and/or progesterone)-positive/HER2-negative BC, NSCLC (including adenocarcinoma and squamous cell subtypes), OEC, and HNSCC; and Parts A mTPI-2 cohort, C1, and D1: BC, NSCLC (including adenocarcinoma and squamous cell subtypes), and HNSCC; Criterion specific to Parts B, C, and D: Subjects must have received the standard prior treatments for metastatic or advanced unresectable disease as outlined below, but not more than 3 (=3) prior lines in total; 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 required for dose escalation (Part A) and measurable disease per RECIST v1.1 required for Parts A2, B, C1, C2, D1 and D2 4. Subjects with treated brain metastases are eligible if the brain metastases are stable and the subject does not require radiation therapy, or steroids. Active screening for brain metastases (eg, brain computed tomography or magnetic resonance imaging) is not required; 5. At least 18 years 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 = 9.0 g/dL (without transfusion within 30 days of Cycle 1 Day 1); AST, ALT, and alkaline phosphatase (ALP) =2.5 g/dL. 9. Women of childbearing potential (defined as women who have experienced menarche and who are not permanently sterile or postmenopausal; postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause), and males must agree to use a highly effective method of contraception prior to study entry, while on study drug and for a period of 50 days after the last dose of
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 antibiotic, antiviral or antifungal therapy within 2 weeks of study enrollment - history of or current active autoimmune diseases, including but not limited to myasthenia gravis, inflammatory bowel diseases, RA, autoimmune thyroiditis which is not a sequela of prior immune checkpoint therapy, 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 EGFR or ALK 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 mAb 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: PartA determine safety of CX2009, MTD/RP2D/DLTs of CX2009 given IV every 21d as monotherapy to pts with solid tumors. PartA2:characterize protease activity+measure cleavage of CX2009 in biopsies,blood in pts with high CD166 by IHC, obtain characterization of safety of CX2009 given as monotherapy. PartB:evaluate efficacy of CX2009 given IV every 21d as monotherapy at MTD/RP2D in pts with solid tumors (high CD166 by IHC). PartC1:determine safety of CX2009,MTD/RP2D/DLTs of CX2009 given IV every 14d as monotherapy to pts with solid tumors (high CD166 by IHC) PartC2:evaluate clinical activity of CX2009 given IV every 14d as monotherapy at MTD/RP2D to pts in an indication specific cohort high CD166 by IHC. Part D1:determine safety,MTD/RP2D/DLT's of CX2009 in comb with CX072 both given IV every 14d Part D2 evaluate efficacy of CX2009 in comb. with CX072 given IV every 14d at MTD/R2PD to subjects PDL1+ and high CD166 by IHC.;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; Obtain additional characterization of the safety of CX-2009 at the MTD/RP2D; Evaluate efficacy in subjects treated with CX-2009 as monotherapy. Evaluate preliminary efficacy in subjects treated with CX-2009 and CX-072 Characterize PK of CX-2009 when administered in combination with CX-072 Assess incidence of ADA formation to CX-2009 when it's administered in combination with CX-072 Characterize the PK profile of CX-072 when it's administered in combination with CX-2009 Assess the incidence to ADA formation to CX-072 when it's administered with CX-2009 Obtain additional characterization of safety of CX-2009 when administered with CX-072 at MTD/RP2D Evaluate Efficacy of CX-2009 + CX072;Primary end point(s): Dose-limiting toxicities Study-drug related AEs and AEs leading to discontinuation Changes from baseline in clinica | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part A The secondary objectives of Part A are: •Evaluate preliminary efficacy in subjects treated with CX-2009 as monotherapy on the basis of: ORR by the RECIST Version 1.1, Time to tumor response (TTR), Duration of response (DOR), Progression-free survival (PFS), Overall survival (OS) •Characterize PK of CX-2009 with respect to the following analytes: - Intact CX-2009 (referring to the prodrug form of CX-2009 DM4) - Total CX-2009 (intact and activated forms of CX-2009 DM4) - Total CX-2009-conjugated DM4 (antibody conjugated-DM4) - Free DM4 - S-methyl DM4 (DM4-Me), a DM4 metabolite with potent cytotoxic activity; •Assess the incidence of ADA formation to CX-2009 Part A2 The secondary objectives of Part A2 are to determine: •Evaluate preliminary efficacy in subjects treated with CX-2009 as monotherapy on the basis of: - ORR by the RECIST Version 1.1; TTR; DOR; PFS; and OS •Characterize the PK of CX-2009 with respect to the following analytes: - Intact CX-2009 - Total CX-2009 - Total CX-2009-conjugated DM4 - Free DM4 - DM4-Me •Assess the incidence of ADA formation to CX-2009 Part B The secondary objectives of Part B are to: •Obtain additional characterization of the safety of CX-2009 at the MTD/RP2D •Evaluate efficacy in subjects treated with CX-2009 as monotherapy on the basis of: - DOR; TTR; PFS; and OS •Characterize the PK of CX-2009 with respect to the following analytes: - Intact CX-2009 - Total CX-2009 - Total CX-2009-conjugated DM4 - Free DM4 - DM4-Me •Assess the incidence of ADA formation to CX-2009 Part C1 The secondary objectives of Part C1 are •Evaluate preliminary clinical activity in subjects treated with CX-2009 as monotherapy on the basis of: - ORR by the RECIST Version 1.1;TTR; DOR; PFS; and OS; •Characterize the PK of CX-2009 with respect to the following analytes: - Intact CX-2009 - Total CX-2009 - Total CX-2009-conjugated DM4 - Free DM4 - DM4-Me •Assess the incidence of ADA | — |
Countries
Germany, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Team
CytomX Therapeutics, Inc
Outcome results
None listed