ADVANCED OR RECURRENT SOLID TUMORS OR LYMPHOMAS MedDRA version: 19.0 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 19.0 Level: PT Classification code 10025310 Term: Lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Code: CX-072
Pharmaceutical Form: Solution for infusion
Current Sponsor code: CX-072
Other descriptive name: CX-072
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Sponsors
CytomX Therapeutics, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed diagnosis of the following metastatic or advanced unresectable tumors that progressed on standard therapy: • Part A: any metastatic or advanced unresectable solid tumor or lymphoma, measurable or non-measurable disease allowed, no further standard of care therapy available o Naïve to treatment with a PD-1/PD-L1 inhibitor o No PD-1/PD-L1 inhibitor therapy available for their specific disease in the country where they are being treated • Part B1: any metastatic or advanced unresectable solid tumor or lymphoma, measurable or non-measurable disease allowed, no further standard of care therapy available o Naïve to treatment with a PD-1/PD-L1 inhibitor o No PD-1/PD-L1 inhibitor therapy available for their specific disease in the country where they are being treated o Naïve to treatment with a CTLA-4 inhibitor • Part B2: any metastatic or advanced unresectable solid tumor or lymphoma with measurable disease allowed, no further standard of care therapy available o Previous treatment with a PD-1/PD-L1 inhibitor o Discontinued treatment with PD-1/PD-L1 inhibitor for reasons other than toxicity o Naïve to treatment with a CTLA-4 inhibitor o Agreement to participate in biomarker analysis and have tumor suitable for biopsy (only in cohorts receiving CX-072 + 3 mg ipilimumab [but not 10 mg ipilimumab]) • Part C: metastatic or advanced unresectable melanoma with BRAF V600E mutation-positive as detected by a diagnostic approved test (in the region where the subject is treated), measurable or non-measurable disease allowed o Naïve to treatment with BRAF-inhibitor o Naïve to treatment with a PD-1/PD-L1 inhibitor • Part D: metastatic or advanced unresectable gastric and GEJ cancers, measurable disease required o Naïve to treatment with a PD-1/PD-L1 inhibitor o Subjects that have had their tumor tissue analyzed for PD-L1 may not enroll if they are known to be PD-L1 negative. (Subjects known to be PD-L1 positive or that have never undergone PD-L1 tumor assessment are eligible.) o HER2 negative (FISH or IHC testing acceptable) o For GEJ tumors with significant esophageal component, esophageal cancer Siewert II/III o Subjects must be ineligible for platinum based or fluorpyrimidine based chemotherapy or approved ramucirumab based regimen or have already received these therapies. Subjects must have had standard of care surgery for their cancer, if applicable. 2. Agreement to provide mandatory archival tissue or fresh biopsy. A tumor biopsy is required at baseline if there is no other record of histological diagnosis of tumor. 3. For subjects in Part B2 receiving 3 mg/kg of ipilimumab and those who agree to participate in the biomarker analysis and who have a tumor site that is safe to biopsy, subjects must have a biopsy within 90 days of study entry and be willing to undergo at least one on-treatment tumor biopsy. 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 [CT] or magnetic resonance imaging [MRI]) is not required. 5. At least 18 years of age. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 7. Anticipated life expectancy of at least 3 months. 8. Screening laboratory values must meet the following criteria: • White blood cells (WBCs) > 2000/µL or 2.0 × 10(-9)/L; • Neutrophils = 1500/µL or 1.5 × 10(-9)/L; • Platelets = 100 × 10(-
Exclusion criteria
Exclusion criteria: 1. Prior therapy with a chimeric antigen receptor (CAR) T-cell containing regimen. 2. Baseline QTc is > 470 ms in the vemurafenib treatment arm, or taking any medication known to prolong the QT interval. 3. Prior history of myocarditis irrespective of the cause. 4. Treatment with strong CYP3A4 inhibitors or inducers, as well as use of CYP1A2 substrates with a narrow therapeutic window assigned to the vemurafenib treatment arm. http://medicine.iupui.edu/clinpharm/ddis/main-table/ 5. History of severe allergic or anaphylactic reactions to human monoclonal antibody therapy or known hypersensitivity to any Probody Tx. 6. Active or history of uveal, mucosal, or ocular melanoma is excluded in Parts B2 and C. 7. Subjects with gastrostoma are excluded in Part D. 8. Human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS)-related illness, chronic hepatitis B or C. 9. History of or current active autoimmune diseases, including but not limited to inflammatory bowel diseases, rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis, systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies, or type 1 insulin dependent diabetes mellitus. 10. History of syndrome or medical condition(s) that requires systemic steroids (> 10 mg daily prednisone equivalents) or immunosuppressive medications. 11. History of allogeneic tissue/solid organ transplant, prior stem cell or bone marrow transplant. 12. Chemotherapy, biochemotherapy, radiation or immunotherapy or any investigational treatment within 30 days prior to receiving any study drug. 13. Major surgery (requiring general anesthesia) within 3 months or minor surgery (excluding biopsies conducted with local/topical anesthesia) or gamma knife treatment within 14 days (with adequate healing) of administration of any study drug. 14. Unresolved acute toxicity of the NCI CTCAE v4.03 Grade > 1 (or baseline, whichever is greater) from prior anti-cancer therapy. Alopecia and other non-acute toxicities are acceptable. 15. 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 and considered to have been cured and in the opinion of the Investigator, present a low risk for recurrence. These exceptions include, but are not limited to, basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix or breast. 16. Received a live vaccine within 30 days prior to first dose of study drug. 17. Known pre-existing condition of age-related macular degeneration (AMD). 18. Uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection (including fever within 48 hours of screening), symptomatic congestive heart failure (ie, New York Heart Association Class III or IV), unstable angina pectoris, clinically significant and uncontrolled cardiac arrhythmia, non-healing wound or ulcer, or psychiatric illness/social situations that would limit compliance with study requirements. 19. Participating in an ongoing clinical study involving treatment with medications, radiation or surgery. 20. Women who are pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. Evaluate the safety and tolerability of multiple doses of CX-072, administered as monotherapy or in combination with ipilimumab or vemurafenib to subjects with metastatic or locally advanced unresectable solid tumors or lymphomas. 2. Determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of: • CX-072 as a monotherapy administered to PD-1/PD-L1 naïve subjects, • CX-072 in combination with ipilimumab (concomitant schedule) administered to PD-1/PD-L1 and CTLA-4 inhibitor naïve subjects, • CX-072 in combination with ipilimumab (phased schedule) administered to subjects that have had prior treatment with a PD-1/PD-L1 inhibitor, and • CX-072 in combination with vemurafenib administered to PD-1/PD-L1 naïve subjects. ;Secondary Objective: 1. Obtain preliminary evidence of anti-cancer activity on the basis of objective responses in subjects treated with CX-072 as monotherapy or when administered in combination with ipilimumab or vemurafenib: • Objective response rate by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1 and irRECIST), • Objective response rate by modified immune-related response criteria as defined in the Common Core Document or Modified Cheson/Lugano Classification for Lymphomas, • Time to response (TTR) • Duration of response (DOR) • Progression-free survival (PFS) Similarly, obtain preliminary evidence of anti-cancer activity on the basis of objective responses in subjects treated with CX-072 as monotherapy in advanced or metastatic gastric and gastroesophageal junction (GEJ) tumors 2. Characterize the immunogenicity of CX-072 3. Characterize the preliminary single and multi-dose pharmacokinetic profile of CX-072 4. Assess overall survival (OS) in subjects receiving CX-072;Primary end point(s): 1. Assessment of dose limiting toxicity (DLT) 2. Establishment of the maximum tolerated dose (MTD). ;Timepoint(s) of evaluation of this end point: LPLV | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Objective response rate by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1 and irRECIST) 2. Objective response rate by modified immune-related response criteria as defined in the Common Core Document or Modified Cheson/Lugano Classification for Lymphomas 3. Time to response (TTR), 4. Duration of response (DOR) 5. Progression-free survival (PFS);Timepoint(s) of evaluation of this end point: LPLV | — |
Countries
France, Germany, Hungary, Netherlands, Poland, Spain, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Trial Team
CytomX Therapeutics, Inc
Outcome results
None listed