A phase 1-2, first-in-human study of CX-2029 in adults with advanced solid tumors which cannot be removed completely through surgery, or cancer of B cells, a type of white blood cell responsible for producing antibodies.
- Conditions
- Metastatic or locally advanced unresectable solid tumor or diffuse large B-cell lymphomaMedDRA version: 20.0 Level: HLT Classification code 10012819 Term: Diffuse large B-cell lymphomas System Organ Class: 100000004851MedDRA version: 20.0 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: PT Classification code 10067821 Term: Head and neck cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: LLT Classification code 10033606 Term: Pancreatic cancer non-resectable System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-001456-34-ES
- Lead Sponsor
- CytomX Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 202
Inclusion Criteria for All Study Parts (Parts A, B, and C):
1. At least 18 years old
2. Ability and willingness to sign an informed consent form (ICF)
3. Screening laboratory values must meet the following criteria:
- Absolute neutrophil count =1500/µL
- Platelet count =100 × 10^3/µL (no transfusion within 2 weeks)
- Hemoglobin =10.0 g/dL (no transfusion within 2 weeks)
- Creatinine =1.5 × institution’s upper limit of normal (ULN)
- Both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 × institution’s ULN
- Total bilirubin =1.5 × ULN (total bilirubin must be =3 × institution’s ULN in subjects with Gilbert’s syndrome)
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. Subjects with NSCLC:
- Must have received prior treatment with platinum-based therapy and a PD-1/PD-L1 inhibitor. A checkpoint inhibitor should have been administered if approved for the subject’s indication in their locality, alone or in combination with other therapy
- Subjects with advanced or metastatic stage IV NSCLC with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic alterations are eligible if they have progressed on treatment or did not tolerate appropriate targeted therapy. This would include osimertinib for T790M mutation-positive NSCLC
- Subjects with NSCLC with known ROS1 rearrangement must have received prior treatment with crizotinib
6. Females of childbearing potential and non-sterile males must agree to practice highly effective methods of birth control for the duration of the study and for 6 months after the last dose of study drug
Inclusion Criteria Specific for Part A, Part B, or Part C
Part A:
1. Histologically or cytologically confirmed metastatic or locally advanced unresectable solid tumor
2. Documented progression or relapse after at least 1 prior systemic therapy. Moreover, subjects must have exhausted available life prolonging therapies
3. Measurable or evaluable per RECIST v1.1
4. Eastern Cooperative Oncology Group (ECOG) 0 to 1
5. Agreement 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
Part B
1. Histologically or cytologically confirmed metastatic or locally advanced unresectable HNSCC, DLBCL, NSCLC, or pancreatic cancer
2. Subjects with HNSCC must have received a platinum-containing regimen and a PD-1 inhibitor if approved for the subject’s indication in the subject’s locality
3. Relapsed or refractory DLBCL after 2 lines of systemic therapy. At least 1 line should contain anti-CD20-based immunochemotherapy, and subjects should not be candidates for autologous hematopoietic stem cell transplantation
4. Subjects with pancreatic cancer should have rece
1. Neuropathy >Grade 1
2. Serious concurrent illness, including, but not limited to, the following:
- Clinically-relevant infection, including known active hepatitis B or C, human immunodeficiency virus, or non-viral infection requiring antibiotics
- Significant cardiac disease, such as recent myocardial infarction (=6 months prior to Day 1), unstable angina pectoris, uncontrolled congestive heart failure (New York Heart Association >Class II), uncontrolled hypertension (NCI CTCAE Version 5.0 Grade 3 or higher), uncontrolled cardiac arrhythmias, 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 clinically significant 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
- Hepatic impairment which is moderate (Child-Pugh B) or severe (Child-Pugh C)
- Severe renal impairment (creatinine clearance [CrCl] <30 mL/min)
3. Concurrent systemic treatment with an anticancer biologic within 30 days prior to receiving study drug or with a non-biological anticancer drug within 14 days prior to receiving study drug
4. History of severe allergy or anaphylactic reaction to previous monoclonal antibodies or known hypersensitivity to auristatins
5. Unresolved acute toxicity NCI CTCAE Version 5.0 >Grade 1 (or baseline, whichever is greater) from prior anticancer therapy. Alopecia and other non-acute toxicities are acceptable
6. History of malignancy within the previous 2 years except for localized basal cell or squamous cell skin cancers, superficial bladder cancers, or carcinoma in situ of the prostate, cervix, or breast
7. Concurrent anticoagulation with warfarin
8. Inability to discontinue treatment with a strong CYP3A4 inhibitor or strong CYP3A4 inducer prior to start of treatment
9. Clinically significant iron metabolism disorders (eg, sickle cell anemia)
10. Transfusion dependent anemia with transfusion dependency of =3 months
11. Use of iron chelators
12. Major surgery within 3 months prior to study enrollment
13. Live vaccine within 28 days prior to planned dose
14. Participation in an ongoing clinical study involving medications, radiation, or surgery
15. Women who are pregnant or breast-feeding
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