A clinical trial of CX-072 (study drug) as monotherapy and in combination with YERVOY® (IPILIMUMAB) or with ZELBORAF® (VEMURAFENIB), which are already approved drugs in many countries, in patients with advanced or recurrent solid tumors or lymphomas.
- Conditions
- ADVANCED OR RECURRENT SOLID TUMORS OR LYMPHOMASMedDRA version: 20.0Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]MedDRA version: 20.0Level: PTClassification code 10025310Term: LymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
- Registration Number
- EUCTR2016-002490-36-PL
- Lead Sponsor
- CytomX Therapeutics, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 330
All subjects must have histologically confirmed diagnosis of metastatic or advanced unresectable tumors that progressed on standard therapy.
Inclusion criteria for subjects in each specific Part:
-Part A: any metastatic or advanced unresectable solid tumor or lymphoma, measurable or nonmeasurable disease allowed, no further SOC therapy available
o Immunotherapy naive, including PD-1/PD-L1 and CTLA-4 inhibitor therapy naive
-Part A2: any metastatic or advanced unresectable solid tumor or lymphoma, measurable disease allowed, no further SOC therapy available
o TPS = 1% membranous staining based on the DAKO PD-L1 IHC 22C3 pharmDxo
o Immunotherapy naive, including PD-1/PD-L1 and CTLA-4 inhibitor therapy naive (where there is no immunotherapy or PD-1/PD-L1 and CTLA-4 inhibitor therapy available for their specific disease in the country where they are being treated)
o Agreement to participate in biomarker analysis and have a tumor site that is safe to biopsy.
-Part B1: any metastatic or advanced unresectable solid tumor or lymphoma, measurable or nonmeasurable disease allowed, no further SOC therapy available
o Immunotherapy naive, including PD-1/PD-L1 and CTLA-4 inhibitor therapy naive
• Part B2: any metastatic or advanced unresectable solid tumor or lymphoma with measurable disease allowed, no further SOC 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 Naive to treatment with a CTLA-4 inhibitor
o Agreement to participate in biomarker analysis and have tumor safe to biopsy
• 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 nonmeasurable disease allowed
o Naive to treatment with BRAF-inhibitor
o Immunotherapy naive, including PD-1/PD-L1 and CTLA-4 inhibitor therapy naive
• Part D: measurable disease is required
o Must be willing to provide a blood sample at Screening for hTMB testing; and
o Immunotherapy naive, including PD-1/PD-L1 and CTLA-4 inhibitor therapy naive (where there is no available life-prolonging immunotherapy or PD- 1/PD- L1 and CTLA-4 inhibitor therapy available for their specific disease in the country where they are being treated) of the following tumor types (tumor specific criteria listed in the protocol):
-UPS
-Small bowel adenocarcinoma
-cSCC
-MCC
-Thymic carcinoma
-Anal SCC
-TNBC
-hTMB
Inclusion criteria for all subjects in all Parts:
1. 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.
2. For subjects in Part A2 and B2 (for Part B2, only those subjects 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.
3. 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.
4. At least 18 years of age.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Anticipated life expectancy of at least 3 months.
7. Screening
1. Prior therapy with a chimeric antigen receptor (CAR) T-cell containing regimen.
2. Baseline QTc is > 470 ms, or taking any medication known to prolong the QT interval.
3. Prior history of myocarditis irrespective of the cause.
4. Treatment with strong cytochrome P450 (CYP) 3A4 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 thymic epithelial tumor, thymoma, or thymic carcinoma gastrostoma are excluded in Part B1 and B2.
8. Human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS)-related illness, chronic hepatitis B or C; subjects with HIV that have an undetectable viral load and a CD4 cell count > 400/mL and who remain on antiretroviral regimen will be eligible for enrollment into Part D anal SCC and hTMB cohorts;
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 (except for subjects in Part B2) or any investigational treatment within 30 days prior to receiving any study drug.
13. Subjects in Part C cannot have a glomerular filtration rate ? 60;
14. Subjects in Part B2 cannot have received immunotherapy within 14 days prior to receiving study drug.
15. 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.
16. Unresolved acute toxicity of the NCI CTCAE v4.03 Grade > 1 (or baseline, whichever is greater) from prior anti-cancer therapy. Alopecia and other nonacute toxicities are acceptable.
17. 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.
18. Received a live vaccine within 30 days prior to first dose of study drug.
19. Known pre-existing condition of age-related macular degeneration.
20. Intercurrent illness, including, but not limited to symptomatic congestive heart failure (ie, New York Heart Association Class III or IV), unstable angina pectoris, clinically significant and uncontrolled cardiac arrhythmia, nonhealing wound or ulcer, or psychiatric illness/social situations that would limit compliance with study requirements.
21. Ongoing or active infection (including fever within 48 hours of
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