Open label, First in human study for CX-2009 in adults with metastatic or locally advanced unresectable solid tumors
- Conditions
- Metastatic or locally advanced unresectable solid tumors in followingindications: breast cancer (BC), castrate-resistant prostatecarcinoma (CRPC), non-small cell lung carcinoma (NSCLC), ovarian epithelial cancer (EOC), endometrial carcinoma (EC), head and neck squamouscell carcinoma (HNSCC), or cholangiocellular carcinoma (CCC)MedDRA version: 21.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-000625-12-NL
- Lead Sponsor
- CytomX Therapeutics, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 563
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 <= 1.5 x institution upper limit of
normal (ULN); aspartate aminotransferase (AST) <= 2.5xinstitution's
ULN; alanine aminotransferase (ALT) <= 2.5x institution's ULN (AST,
ALT <5 x ULN for subjects with CCC and liver metastases); and serum
total bilirubin <= 1.5x institutional ULN (total bilirubin must be <=3x
institution's ULN in subjects with Gilbert's syndrome). Serum total
bilirubin <= 3.0 x institutional ULN for subjects with CCC and liver
metastasis
For Parts B, C, D only: Hemoglobin >= 9.0 g/dL (without transfusion
within 30 days of Cycle 1
Day 1); AST, ALT, and alkaline phosphatase (ALP) <=2.5 × institution's
ULN (without exemption for liver or bone metastases); International
normalized ratio (INR) and activated partial thromboplastin time
(aPTT) <= 1.5 × ULN (unless subject is on therapeutic anticoagulation,
at which time the INR and aPTT must be in the target therapeutic
anticoagulation range); and Serum albumin >=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
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 (<= 6 months prior to day 1), unstable angina pectoris, uncontrolled congestive heart failure (NY Heart association >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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method