A Phase 1 Multiple Dose, Dose Escalation Trial of AEB1102 (CO-Argl-PEG) in Patients with Advanced Solid Tumors.
- Clements University Hospital
- UT Southwestern Ambulatory Services
- Zale Lipshy University Hospital
David Gerber, M.D.
This is a Phase 1 multiple dose, dose escalation trial in patients with advanced solid tumors who have failed or cannot tolerate standard therapies.
Study Population: up to 48 patients may be enrolled in the dose escalation portion (Part 1) of the trial and up to 75 patients may be enrolled in the expansion portion (Part 2) of the trial.
Part 1 : Dose escalation Phase - to determine the safety and maximal tolerated dose of the study drug, aeB1102
Cohorts of 3 to 6 patients each will be sequentially assigned to receive escalating dose levels of aeB1102 (Co-argi-PeG) by slow intravenous (iV) injection, weekly, for 4 weeks (one cycle).
uTSW will participate in Part 2:
Part 2: Dose expansion Phase - to further evaluate the safety of the maximal tolerated dose as determined during the dose escalation phase. The phase will consist of an additional 3 groups of 20-25 patients with a specific subtype of solid tumor. They will receive aeB1102 at the maximal or the optimal biologic dose.
all patients in both parts of the trial will be monitored for safety by periodic physical exams, vital signs, eCGs, hematology, and chemistry laboratory testing and by testing for antibodies to both aeB1102 and polyethylene glycol (PeG). adverse events will be recorded at each study visit.
Tumor assessment by contrast-enhanced CT/CT-PeT, or MRi will be performed at baseline, 2 months and every 3 months thereafter.
A patient must meet all of the following criteria to be enrolled in this study:
1) Has an advanced solid tumor that has relapsed or progressed after, or inability to tolerate, standard therapy for the disease, or for which a standard therapy does not exist, and as such is considered a candidate for Phase 1 treatment.
2. Is 18 years of age or older
3. Has adequate organ function defined as follows:
a. Bone Marrow: Hemoglobin >=9 g/dL; absolute neutrophil count (ANC) >=1.5x109/L; platelet count >=100,000/[MICRO-SYMBOL]L; transfusion (RBC, platelets) independent at least 14 days before first dose
b. Hepatic function: transaminase levels (aspartate aminotransferase [AST]/alanine
aminotransferase [ALT] < 2.5-times ULN, < 5x ULN in patients with liver metastases; total bilirubin <2.0 mg/dL;
c. Renal: serum creatinine <= 1.5x ULN
4. Eastern Cooperative Oncology Group (ECOG) performance score 0-2 (See Protocol Appendix 1)
5. If female and of child-bearing potential, has a negative serum pregnancy test within 7 days of Day 1
6) If sexually active (male or female), must be surgically sterile, post-menopausal (defined as female patient with 12 months of spontaneous amenorrhea, or 6 months of spontaneous amenorrhea with serum FSH levels higher than 40 mIU/ml, or 6 weeks after bilateral surgical oophorectomy), or must agree to use a physician-approved method of birth control for the duration of the study and for a minimum of 28 days after the last study drug administration
7. Is able and willing to understand the requirements and risks of the study and to sign a written informed consent form prior to any study-related procedures
SPECIFIC INCLUSION CRITERIA FOR EXPANSION GROUPS:
For All Dose Expansion Groups:
A patient must meet all of the following criteria to be enrolled in Part 2 of this study:
1) Has measurable disease based on RECIST 1.1 as determined by the treating investigator.
Tumor lesions in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
2) If required, consent to core needle or incisional biopsy (please refer to schedule of events for details)
3) Recovery of toxicities related to any prior treatments, including but not limiting to prior anticancer therapy or therapies received as anticancer (e.g. systemic therapy, radiotherapy, surgery), such as symptom control or palliative, therapeutic intention as part of a clinical trial, to at least Grade 1 by CTCAE v 4.03. Exceptions are patients with adverse event(s) that are
clinically non-significant and/or stable on supportive therapy. These patients are allowed to participate with prior approval by the sponsor
Specific for Cutaneous Melanoma:
1) Histologically or cytologically confirmed unresectable, locally advanced or metastatic
(American Joint Committee on Cancer [AJCC] stage IIIB, IIIC, or IV) cutaneous malignant melanoma
2) Relapsed or progressive disease after or unable to tolerate, at least one prior systemic anticancer regimen for metastatic disease involving immunotherapy (anti-PD-1, anti-PD-L1, or anti-CTLA-4)
3) In patients with tumors that have a relevant BRAF mutation, relapsed, refractory, or unable to tolerate at least one prior systemic anticancer regimen for metastatic disease involving a BRAF inhibitor
Specific for Uveal Melanoma:
1) Uveal melanoma with histologically or cytologically-proven metastatic disease
Specific for Small Cell Lung Cancer:
1) Extensive disease (ED) per criteria of the International Association for the Study of Lung Cancer (IASLC)-American Joint Committee on Cancer (AJCC) TNM staging system
2) Relapsed or progressive disease after, or inability to tolerate, at least one prior platinum-based chemotherapy regimen for metastatic disease