In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 3_suppl ( 2015-01-20), p. 338-338
Abstract:
338 Background: PF-04136309 (a novel CCR2 inhibitor) has shown anti-tumor activity in the preclinical setting in PC by depleting inflammatory monocytes and tumor associated macrophages (TAM) that contribute to an immunosuppressive tumor microenvironment. We hypothesized that combining PF-04136309 with FOLFIRINOX may improve clinical outcomes in PC. Methods: This is a phase Ib study with a dose de-escalation schema given the minimal toxicity of PF-04136309. The study includes Arm A (FOLFIRINOX only), Arm B (FOLFIRINOX plus PF-04136309) and an expansion cohort at the rapid phase II dose (RP2D). FOLFIRINOX (oxaliplatin 85 mg/m 2 , irinotecan 180 mg/m 2 , LV 400 mg/m 2 , 5FU bolus 400 mg/m 2 and 2,400 mg/m 2 over 46 hours) was administered every two weeks. PF-04136309 at 500 mg twice daily via oral route was the starting dose level for Arm B. Treatment response was assessed after 6 cycles of treatment. Bone marrow biopsy and EUS/FNA at baseline and post 2 cycles were performed to assess the impact of treatment on the prevalence and function of inflammatory monocytes in the blood, bone marrow and tumor. Results: A total of 41 patients have been enrolled in the study to date (6 in Arm A, 8 in Arm B and 27 in the expansion cohort). The mean age of patients was 61.1 (range 45-75 yrs), male/female: 21/20, Caucasian/others: 32/9, borderline/locally advanced: 7/34. PF-04136309 at the starting dose did not result in additional toxicities when combined with FOLFIRINOX and it is the RP2D. Out of 35 patients treated with FOLFIRINOX plus PF-04136309, 6 are still in treatment, 6 are non-evaluable (withdrew consent or had poor tolerance). Of the 23 evaluable patients, 21 (91.3%) completed all 6 cycles; 12 (52.2%) had PR by RECIST and 11 (47.8%) had SD. Curative resections were achieved in 4 out of 5 with borderline resectable and 2 with locally advanced PC. Moreover, blockade of TAM mobilization was demonstrated by FACS and qPCR analysis of baseline and post-treatment FNA biopsies. Conclusions: Combing PF-04136309 with FOLFIRINOX is safe and tolerable. The regimen resulted in impressive treatment response and it further validated CCR2 inhibition in PC. Survival data and more correlative science will be forthcoming. Clinical trial information: 01413022.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2015.33.3_suppl.338
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2015
detail.hit.zdb_id:
2005181-5
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