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S. Demas
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P2.06 - Poster Session with Presenters Present (ID 467)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.06-006 - Phase I/II Dose Escalation Study of L-DOS47 as a Monotherapy in Non-Squamous Non-Small Cell Lung Cancer Patients (ID 4455)
14:30 - 14:30 | Author(s): S. Demas
- Abstract
Background:
L DOS47, a cancer therapeutic designed to exploit the acidic tumour extracellular environment, is a protein conjugate consisting of a urease conjugated to a camelid monoclonal antibody (AFAIKL2) that is targeted to the CEACAM6 antigenic tumour marker. The AFAIKL2 antibody serves as a targeting agent to deliver the enzyme to the tumor sites while the urease enzyme converts urea, an abundant natural metabolite, into ammonia and generates a local pH increase. The combined effect of ammonia toxicity and pH increase is cytotoxic to cancer cells in culture and in xenograft models. This first in human study of L DOS47 was designed to define the maximum tolerated dose of multiple doses of L-DOS47 administered intravenously to patients with non-squamous NSCLC when given as a monotherapy.
Methods:
Stage IIIb or IV histologically confirmed non-squamous NSCLC patients (aged ≥18 yrs, ECOG PS ≤2) receive multiple cycles of L-DOS47 during the study treatment period. L-DOS47 is administered once weekly over 14 days followed by 7 days rest in each treatment cycle. Patients are recruited into cohorts and received the same dose of L-DOS47 on Days 1 and 8 of each treatment cycle. Dose levels of L-DOS47 are escalated in further cohorts following a review of safety data by the Trial Steering Committee.
Results:
Fifty-five (55) pts (median age 61, 53% male) were enrolled in sixteen cohorts (dose levels: 0.12 to 13.55 µg/kg) in four Polish centers. L-DOS47 was well tolerated at the dose levels reviewed. One (1) DLT was reported in a cohort 13 patient (spinal pain). None of the patients treated to date have had a partial or complete response as defined by RECIST v1.1. Thirty-two (32) patients had an overall response of stable disease after completing two cycles of L-DOS47. Thirteen (13) of the 32 patients had a decrease in the sum of diameters of target lesions. One (1) patient in cohort 9 was dosed for 10 cycles without disease progression.
Conclusion:
L-DOS47 monotherapy is well tolerated at dose levels up to 13.55µg/kg.
