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: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10025310Term: LymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-002490-36-GB
- Lead Sponsor
- CytomX Therapeutics, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 568
All pts must have histologically confirmed diagnosis of metastatic or locally advanced unresectable tumors that progressed or are intolerant to standard therapy.
-Part A: metastatic or advnced unresectable solid tumor or lymphoma,msurable or nonmeasurable disease allowd,no further SOC therapy availble;
•Immunotherapy naive,including PD-1/PD-L1 and CTLA-4 inhibitor therapy naïve
-Part A2:any metastatic or advnced unresectable solid tumor or lymphoma, measrable disease allowed, no further SOC therapy available;
•TPS=1% membranous staining based on the DAKO PD-L1 IHC 22C3 pharmDo
•Immunotherpy naive,including PD-1/PD-L1&CTLA-4 inhibitor therpy naïve
•Agrment to participate in biomrker analysis&have tumor site that is safe to biopsy
-Part B1:any metastatic or advnced unresectable solid tumor or lymphoma, mesurable or nonmesurable disease allowed,no further SOC therapy available
•Immunotherapy naive,including PD-1/PDL1&CTLA-4 inhibitor therpy naïve
-Part B2: metastatic or advanced unresectable solid tumor or lymphoma with measurable disease allowed, no further SOC therapy available
•Previous treatment with PD-1/PD-L1 inhibitor
•Discontinued treatment with PD-1/PD-L1 inhibitor for reasons other than toxicity
•Naive to treatment with CTLA-4 inhibitor
•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 diagnostic approved test,
measurable or nonmeasurable disease allowed
•Naive to treatment with BRAF-inhibitor
oImmunotherapy naive,including PD-1/PD-L1&CTLA-4 inhibitor therapy naïve
-Part D:measurable disease is required
•Must be willing to provide blood sample at Screening for hTMB testing
•Immunotherapy naive,including PD-1/PD-L1&CTLA-4 inhibitor therapy naive(where there is no available life-prolonging immunotherapy or PD- 1/PD- L1&CTLA-4 inhibitor therapy to the pt)of the following tumor:UPS,small bowel adenocarcinoma,cSCC,MCC,Thymic carcinoma,Anal SCC,TNBC,hTMB
-Part E:measurable disease is required•Must be willing to provide blood sample at screening for hTMB testing
•Immunotherapy naive,including PD-1/PD-L1&CTLA-4 inhibitor therapy naive(where there is no available life-prolonging immunotherapy or PD-1/PD-L1&CTLA-4 inhibitor therapy available to the pts of following tumor: UPS,small bowel adenocarcinoma,cSCC,MCC,TET,Anal SCC,TNBC,TNBC with skin lesions
For all A-E Parts:
1.Agreement to provide mandatory archival tissue/fresh biopsy.A tumor biopsy is required at baseline if there is no other record of histological diagnosis of tumor.
2.For pts in PartA2 and B2 (for PartB2, only those subjects receiving 3mg/kg of IPI)&those who agree to participate in biomarker analysis&who have tumor site that is safe to biopsy, pts must have biopsy within 90 days of study entry and be willing to undergo at least 1 on-treatment tumor biopsy.
3.Pts with treated brain metastases are eligible if brain metastases are stable and pt does not require radiation therapy,or steroids.Active screening for brain metastases (eg, brain CT or MRI) is not required
4.At least 18 years of age
5.ECOG performance status of 0 or 1
6. Anticipated life expectancy of at least 3 months.
7.Screening laboratory values must meet following criteria:
•WBCs>2000/µL or 2.0×10(-9)/L
•Neutrophils=1500/µL or 1.5×10(-9)/L
•Platelets=100×10(-3)/µL or 100×10(-9)/L
• Hemoglobin=9.0g/dL or 90.0g/L
•Creatinine=2mg/dL or 176.8µmol/L
•AST=2.5×upper limit of normal (
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 therapeutic.
6. Active or history of uveal, mucosal, or ocular melanoma is excluded in
Parts B2 and C.
7. History of interstitial lung disease for patients with TET are excluded in Part B1 and B2.
8. Human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS)-related illness, acute or chronic hepatitis B or C; patients 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 anal SCC cohorts in Parts D and E and hTMB cohort in Part D;
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, type 1 insulin dependent diabetes mellitus or myasthenia gravis.
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 or immunotherapy or any investigational treatment within 14 days prior to receiving study drug; radiation therapy within 3 months prior to receiving study medication (except for radiotherapy for the purposes of palliation confined to a single field that is not the target lesion).
13. Patients in Part C cannot have a glomerular filtration rate
60mL/min/1.73 m2;
14. 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.
15. Unresolved acute toxicity of the NCI CTCAE v4.03 Grade > 1 (or baseline, whichever is greater) that may put the patient at high risk under the current treatment. Alopecia and other non acute toxicities are acceptable.
16. 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.
17.Received a live vaccine within 30 days prior to first dose of study drug.
18. Known pre-existing condition of age-related macular degeneration.
19. 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 ill
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