Virtual Library
Start Your Search
R.E. Sanborn
Author of
-
+
P2.02 - Poster Session with Presenters Present (ID 462)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P2.02-043 - Randomized Ph II Trial of Allogeneic DPV-001 Cancer Vaccine Alone or with Adjuvant for Curatively-Treated Stage III NSCLC (ID 4640)
14:30 - 14:30 | Author(s): R.E. Sanborn
- Abstract
Background:
Tumor-derived autophagosomes (DRibbles®) are a novel cancer immunotherapy providing cross-protection against related tumors and efficacy against established tumors preclinically. We hypothesize efficacy is via presentation of short-lived proteins (SLiPs) and defective ribosomal products (DRiPs) normally not cross-presented by antigen-presenting cells (APCs). DRibble DPV-001 vaccine packages putative cancer antigens, including 13 from the NCI priority list and TLR 2, 3, 4, 7 and 9 agonist activity into microvesicles, with molecules targeting DRibbles to CLEC9A+ APCs. NSCLC overexpresses an average of 176 proteins found in DPV-001. Many of these antigens have single amino acid variants that may serve as immunogenic mimetopes, or altered peptide ligands.
Methods:
Pts completed curative-intent therapy for stage III NSCLC. Treatment: Induction cyclophosphamide; DPV-001 vaccine every 3 weeks x7; then every 6-weeks x4. Randomization was to DPV-001 alone (Arm A), or with an adjuvant; imiquimod (Arm B), or GM-CSF (Arm C). Peripheral blood mononuclear cells and serum were collected at baseline and at each vaccination. Serum was analyzed for >15 fold increased antibody responses to >9000 human proteins (ProtoArray) from baseline to week 12. 11 pts were to be randomized to each arm, with 15 more enrolled on the arm with the greatest number of >15 fold antibody responses.
Results:
13 pts were enrolled into the randomized phase I portion, when enrollment was stopped due to end of grant term. Arm A: 5 pts; B: 4; C: 4. Median Age: 60 (range 45-76); Male/Female: 6/7. Median vaccines administered: 6 (range 3-11); 2 pts still receiving treatment. Reasons for discontinuation: Disease progression (6); 2 toxicity (1 grade 3 dyspnea possibly related, 1 recurrent grade 1 migratory rash with pruritis, related); 1 noncompliance; 1 for elective surgery (unrelated). Other toxicities were grade 1/2; 1 additional grade 3 fatigue (possibly related). Analysis was limited due to small sample size. Median >15 fold antibody responses for Arm A: 8; B: 43.5; C: 50.5 (ranges 0-9; 41-46; 9-162, respectively). There was a significant difference in antibody response between Arms A and B (P=0.0001).
Conclusion:
Allogeneic DPV-001 vaccine administration was tolerable, and >15 fold antibody responses were documented in all but 1 pt. Greatest antibody responses were seen with vaccine/GM-CSF. For pts who may not respond to anti-PD1 due to lack of endogenous anti-tumor response, vaccination with DPV-001 could potentiate checkpoint inhibitors by inducing anti-tumor response. A combination DPV-001 vaccine with anti-PD1 study in advanced NSCLC is pending. NCT01909752, NCI sponsored trial R44 CA121612
-
+
P2.03a - Poster Session with Presenters Present (ID 464)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P2.03a-014 - A Dose-Finding and Phase 2 Study of Ruxolitinib plus Pemetrexed/Cisplatin for Nonsquamous Non–Small Cell Lung Cancer (NSCLC) (ID 3874)
14:30 - 14:30 | Author(s): R.E. Sanborn
- Abstract
Background:
Dysregulation of the JAK/STAT pathway contributes to abnormal inflammatory responses, oncogenesis, treatment resistance, and poor prognosis in NSCLC. This phase 2 clinical trial evaluated the JAK1/JAK2 inhibitor ruxolitinib+pemetrexed/cisplatin as first-line treatment for patients with stage IIIB/IV or recurrent nonsquamous NSCLC and systemic inflammation (per modified Glasgow Prognostic Score [mGPS]).
Methods:
Key inclusion criteria were mGPS of 1/2 and ECOG performance status ≤1. Part 1, an open-label, 21-day safety run-in, assessed ruxolitinib (15 mg BID [chosen dose for Part 2]) plus pemetrexed (500 mg/m[2] IV on Day 1) and cisplatin (75 mg/m[2] IV on Day 1). Ruxolitinib dose selection for Part 2 required <3 dose-limiting toxicities (DLTs) for 9 evaluable patients. Part 2 randomized patients to ruxolitinib+pemetrexed/cisplatin or placebo+pemetrexed/cisplatin. The trial was terminated early for lack of efficacy in other solid tumor programs in patients with high systemic inflammation.
Results:
All 15 patients enrolled in Part 1 received ruxolitinib 15 mg BID plus pemetrexed/cisplatin. Median age was 64 years; male, 80%; mGPS 1, 80%. Median treatment duration was 140 days. The Table reports Part 1 safety data. Four patients were inevaluable for DLTs (<80% compliance, n=2; disease progression, n=2). No DLTs occurred in 11 evaluable patients. The Part 1 overall response rate (ORR) was 53% (8/15; all partial responses). At study termination, 39 and 37 patients were randomized in Part 2 to ruxolitinib and placebo, respectively. Median treatment duration was 43 days. ORR was 31% (12/39) with ruxolitinib+pemetrexed/cisplatin versus 35% (13/37) with placebo+pemetrexed/cisplatin (all partial responses). The short follow-up duration may limit interpretation of Part 2 efficacy. The Part 2 safety profile was consistent with Part 1 (data to be presented).
*Common all-grade (≥30%) or grade 3/4 (≥10%) events.Table. The Most Common Treatment-Emergent Adverse Events in Part 1 Ruxolitinib+Pemetrexed/Cisplatin (N=15) Event, n (%) All-Grade Grade 3/4 Nonhematologic* Nausea 11(73) 1(7) Fatigue 8(53) 3(20) Vomiting 8(53) 1(7) Constipation 7(47) 0 Diarrhea 7(47) 0 Dizziness 7(47) 0 Peripheral edema 7(47) 0 Decreased appetite 6(40) 0 Pyrexia 6(40) 0 Dyspnea 5(33) 1(7) Pneumonia 4(27) 3(20) Pulmonary embolism 2(13) 2(13) Sepsis 2(13) 2(13) New/worsening hematologic laboratory abnormalities Anemia 13(87) 5(33) Lymphopenia 11(73) 2(13) Leukopenia 9(60) 1(7) Neutropenia 9(60) 5(33) Thrombocytopenia 9(60) 1(7)
Conclusion:
Ruxolitinib 15 mg BID had an acceptable safety profile in combination with pemetrexed/cisplatin as first-line treatment of patients with stage IIIB/IV or recurrent nonsquamous NSCLC.
-
+
P3.02c - Poster Session with Presenters Present (ID 472)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P3.02c-051 - A Pre-Treatment Serum Test Based on Complement and IL-10 Pathways Identifies Patients Benefiting from the Addition of Bavituximab to Docetaxel (ID 7068)
14:30 - 14:30 | Author(s): R.E. Sanborn
- Abstract
Background:
SUNRISE, a global, double-bind, Phase III trial of docetaxel (D) plus bavituximab (B) or D plus placebo (P) in previously treated non-squamous non-small cell lung cancer, demonstrated similar overall survival (OS) in both treatment arms. Mass spectrometry and correlative analysis were used to create a test able to identify a subgroup of patients benefitting from the addition of B to D.
Methods:
Pre-treatment serum samples were available for 197 of the first 200 subjects enrolled in the trial. Mass spectra could be generated for 193 samples using the Deep MALDI method (Duncan et al, ASMS 2013), processed and features (peaks) identified. Mass spectral (MS) features associated with various biological functions were identified using a gene set enrichment analysis approach. Analysis of scores based on these MS feature, subsets indicated that in patients with high complement activation outcome depended on IL-10 activation in D+B but not in D+P. A test using the MS features associated with these functions was created to reliably identify a patient subgroup associated with clinical benefit using modern machine learning methods.
Results:
Complement activation, as assessed by a classifier trained using related MS features, was a prognostic factor in both treatment arms, with high activation associated with poorer clinical outcome (OS HR = 0.54, log-rank p = 0.013 for D+B; OS HR = 0.60, log-rank p = 0.040 for D+P). Within the subgroup with high complement activation [N=50 (D+B); N=54 (D+P)], a second classifier using features related to IL-10 activation was able to isolate a subgroup of patients showing numerical benefit from the addition of B [median OS 5.9 months (D+P), 12.5 months (D+B)]. The remaining subgroup showed no benefit from addition of B [median OS 10.4 months (D+P), 5.6 months (D+B)]. Blinded validation of the test in the remainder 397 patients randomized in SUNRISE is will be presented.
Conclusion:
Proteomic and correlative approaches identified complement activation and low IL-10 levels as important pathways for predicting improved outcomes of patient treatment with D+B, in line with preclinical work on B’s mechanism of action. The test resulting from this work will undergo blinded independent validation.
