Ipilimumab and Gemcitabine for Advanced Pancreatic Cancer: A Phase Ib Study

4052 Background: The combination of gemcitabine (gem) and nab-paclitaxel (nab) has demonstrated promising activity in advanced pancreatic cancer. Erlotinib (erl) adds modest benefit to gemcitabine. We initiated this phase IB study to evaluate the safety of the three drug combination and obtain preliminary evidence of efficacy. Methods: Patients (pts) with previously untreated locally advanced (la) or metastatic (met) pancreatic cancer with ECOG PS 0-1 were treated with gem and nab IV days 1,8,15 and once daily erl days 1-28 Q28 days. Standard 3+3 design was used with dose levels (DL) (gem,nab,erl): 1(1,000, 125, 100), -1 (1,000, 100, 100), -2 (1,000, 75, 100), -3 (1,000,75,75). CT scans were obtained Q 2 cycles. DLT was defined as ≥grade (gr) 3 non-hematologic, febrile neutropenia, ≥gr 3 thrombocytopenia, or missing ≥2 doses gem, nab or >5 doses erl within first cycle (C). Results: Nineteen pts were enrolled and completed a total of 62 cycles (range 0-11). Pt characteristics: M/F (9/10), White/Hispanic/AA (15/2/2), median age 63 (range 54-78), ECOG PS 1=11, met/la (12/7). In DL1, 1/3 pts had gr3 dehydration in C 2 and 1/3 had gr 4 neutropenia/sepsis in C 4. Although not formally DLT, 3 more pts were enrolled. Of the next 3 pts, 1 DLT of gr 3 diarrhea/gr 4 neutropenia in C 1 was noted and 1 other pt DC’d therapy for neutropenia after 2 cycles. Of 3 pts in DL -1, 2 DLTs (gr 3 optic neuropathy, too many missed doses) were observed. Of 3 pts in DL -2, 2/3 had DLT (gr 3 esophagitis/fatigue and gr 3 transaminitis). Of 6 evaluable pts in DL -3, no DLTs were observed. Most common gr 3/4 toxicities were neutropenia (9), dehydration, thrombocytopenia (3 each), and hypotension (2). Of 13 pts evaluable for response, 6 had partial response (46%), 5 stable disease (38%), and 2 progressive disease (15%) as best response. Median PFS and OS of entire cohort were 5.3 and 9.3 months respectively. Conclusions: The combination of erlotinib with gemcitabine and nab-paclitaxel is not tolerable at standard single agent dosing of all drugs. However, significant clinical activity was noted, even at DL -3. Further study of the combination will need to incorporate reduced dosing.

Download Full-text

Phase Ib/II study of ALT-803 in combination with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.tps510 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. TPS510-TPS510 ◽

Cited By ~ 1

Author(s):

Jared David Acoba ◽

Amy Rock ◽

Hing C. Wong

Keyword(s):

Pancreatic Cancer ◽

T Cells ◽

Half Life ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Progression Free Survival ◽

Two Stage ◽

Phase Ib ◽

Advanced Phase

TPS510 Background: IL-15 is one of the most promising new candidates in cancer immunotherapy. Similar to IL-2, IL-15 stimulates natural killer (NK) and CD8+ T cells, however IL-15 may be a more effective and safer therapy as it does not trigger regulatory T cells or induce capillary leak syndrome. Preclinical data also show that IL-15 is effective in eradicating murine pancreatic cancers. However, the use of rhIL-15 in the clinic however has been limited by its short half-life (30 minutes) and cytokine related adverse effects, such as fever and hypotension. Compared with IL-15, ALT-803, a novel IL-15 superagonist complex (IL-15N72D:IL-15RαSu/Fc), has a prolonged serum half-life and is capable of potently inducing NK and CD8+ T cell proliferation in vivo. Pancreatic cancer remains one of the most common causes of cancer death and novel therapies are needed. This study represents the first clinical experience of ALT-803 in the treatment of pancreatic cancer. Methods: This is a Phase Ib/II, multi-institution study of ALT-803 in combination with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer. The study involves a phase Ib dose escalation phase to determine the MTD using a standard 3+3 design. Patients will receive gemcitabine 1,000 mg/m2 and nab-paclitaxel 125 mg/m2 D1, 8, 15 and ALT-803 at assigned dose on D2, 9, 16 of a 28d cycle. Primary endpoints are safety and tolerability. Phase II will be a two-stage expansion phase using a Simon two-stage design with a primary endpoint of survival at 8.5 months. Secondary endpoints include response rate, progression free survival, and overall survival. Response will be assessed q8 weeks by RECIST v1.1. Major inclusion criteria include: locally advanced (Phase Ib only) or metastatic pancreatic adenocarcinoma, adequate organ function, PS ECOG 0-2, and 0 or 1 (Phase Ib only) line of prior therapy for advanced pancreatic cancer. Prior nab-paclitaxel is not allowed Current enrollment: Enrollment to the first dose level is ongoing. Complete accrual of phase Ib is expected within nine months. Clinical trial information: NCT02559674.

Download Full-text

Abstract LB-003: High complete and partial response rate in a phase Ib pilot trial with cisplatin plus albumin-bound paclitaxel and gemcitabine in patients with advanced pancreatic cancer

10.1158/1538-7445.am2015-lb-003 ◽

2015 ◽

Cited By ~ 1

Author(s):

Gayle S. Jameson ◽

Erkut Borazanci ◽

Elizabeth Poplin ◽

Michael T. Barrett ◽

John Crowley ◽

...

Keyword(s):

Pancreatic Cancer ◽

Partial Response ◽

Response Rate ◽

Pilot Trial ◽

Advanced Pancreatic Cancer ◽

Phase Ib ◽

Partial Response Rate

Download Full-text

A phase Ib/II study of BBI608 combined with weekly paclitaxel in advanced pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.196 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 196-196 ◽

Cited By ~ 3

Author(s):

Tanios S. Bekaii-Saab ◽

Sameh Mikhail ◽

Adrian Langleben ◽

Carlos Becerra ◽

Derek J. Jonker ◽

...

Keyword(s):

Pancreatic Cancer ◽

Disease Control ◽

Response Rate ◽

Advanced Pancreatic Cancer ◽

Disease Control Rate ◽

Weekly Paclitaxel ◽

Cancer Stemness ◽

Dose Escalation Study ◽

Phase Ib ◽

Heavily Pretreated

196 Background: Cancer stemness is thought to be associated with resistance to chemotherapies. BBI608, a first-in-class cancer stemness inhibitor that works through inhibiting the Stat3 pathway, has shown potent synergistic anti-tumor activity with paclitaxel in vivo. In a phase Ib dose escalation study in patients with advanced solid tumors, BBI608 plus weekly paclitaxel was well tolerated and a RP2D of BBI608 480 mg BID was determined. Methods: Patients with heavily pretreated metastatic pancreatic adenocarcinoma were enrolled in a phase Ib/II extension study to assess safety, tolerability, and preliminary anti-cancer activity in patients with this diagnosis. BBI608 was administered orally at a starting dose of 480 mg or 500 mg twice daily along with paclitaxel 80 mg/m2 IV weekly 3 of every 4 weeks. A sample size of 40 set the bounds of the 90% CI at ±10% to 14%, assuming a DCR of 60% to 80%. Safety and efficacy results for the cohort will be presented as late breaking data. Results: 41 patients were enrolled. Patients had received a median of 2 prior lines of treatment including FOLFIRINOX (71%), gemcitabine/nab-paclitaxel (44%), or both (37%). Overall, prior therapy included gemcitabine in 90%, a thymidylate synthetase inhibitor (eg 5FU, capecitabine) in 81%, platinum in 76%, irinotecan in 73%, and taxane in 44%. Protocol therapy was well tolerated. Related grade 3 AE included diarrhea (N = 2, 4.9%), abdominal pain (N = 2, 4.9%), and nausea (N = 1, 2.4%), and were rapidly reversible. For evaluable patients (N = 31), response rate (PR+CR) was 7% and disease control rate (SD+PR+CR) was 52%. In evaluable taxane-naïve patients (N = 19), response rate was 11%, disease control rate was 63%, and 16% were progression free at 24 weeks. Overall (ITT, N = 41) mPFS was 10 weeks and mOS was 24 weeks. For the taxane-naïve patients (ITT, N = 23) mPFS was 16 weeks and mOS was 30 weeks. Conclusions: BBI608 plus weekly paclitaxel has demonstrated safety, tolerability, and promising activity in patients with refractory, heavily pretreated pancreatic cancer; particularly in taxane-naïve patients. Durable disease control and prolonged overall survival in this pre-treated population are notable. Clinical trial information: NCT01325441.

Download Full-text