2. Academic Validation
  3. A multicenter, randomized phase 2 study to establish combinations of CBP501, cisplatin and nivolumab for ≥3rd-line treatment of patients with advanced pancreatic adenocarcinoma

A multicenter, randomized phase 2 study to establish combinations of CBP501, cisplatin and nivolumab for ≥3rd-line treatment of patients with advanced pancreatic adenocarcinoma

  • Eur J Cancer. 2024 Apr:201:113950. doi: 10.1016/j.ejca.2024.113950.
T Enzler 1,  A Nguyen 2,  J Misleh 3,  V J Cline 4,  M Johns 5,  N Shumway 6,  S Paulson 7,  R Siegel 8,  T Larson 9,  W Messersmith 10,  D Richards 11,  J Chaves 12,  E Pierce 13,  M Zalupski 14,  V Sahai 14,  D Orr 15,  S A Ruste 16,  A Haun 16,  T Kawabe 17
Affiliations

Affiliations

  • 1 Rogel Cancer Center, University of Michigan Health, Ann Arbor, MI, USA. Electronic address: tenzler@med.umich.edu.
  • 2 Comprehensive Cancer Centers of Nevada, Henderson, NV, USA.
  • 3 Medical Hematology Oncology Consultants PA, Newark, DE, USA.
  • 4 Texas Oncology - Austin Midtown, Austin, TX, USA.
  • 5 Oncology Hematology Care Eastgate, Cincinnati, OH, USA.
  • 6 Texas Oncology-San Antonio Stone Oak, San Antonio, TX, USA.
  • 7 Texas Oncology - Baylor Charles A. Sammons Cancer Center, Dallas, TX, USA.
  • 8 Illinois Cancer Specialists, Arlington Heights, IL, USA.
  • 9 Minnseota Oncology Hematology PA, Minneapolis, MN, USA.
  • 10 University of Colorado Cancer Center, Aurora, CO, USA.
  • 11 Texas Oncology - Northeast Texas Cancer and Research Institute, Tyler, TX, USA.
  • 12 Northwest Medical Specialties, PLLC, Tacoma, WA, USA.
  • 13 Ochsner MD Anderson Cancer Center, New Orleans, LA, USA.
  • 14 Rogel Cancer Center, University of Michigan Health, Ann Arbor, MI, USA.
  • 15 Mary Crowley Cancer Research, Dallas, TX, USA.
  • 16 Medical Affairs, Veristat LLC, Toronto Canada.
  • 17 CanBas Co., Ltd., Numazu, Shizuoka, Japan.
PMID: 38422585 DOI: 10.1016/j.ejca.2024.113950
Abstract

Background: There is no standard of care for ≥ 3rd-line treatment of metastatic pancreatic adenocarcinoma (PDAC). CBP501 is a novel calmodulin-binding peptide that has been shown to enhance the influx of platinum agents into tumor cells and tumor immunogenicity. This study aimed to (1) confirm efficacy of CBP501/cisplatin/nivolumab for metastatic PDAC observed in a previous phase 1 study, (2) identify combinations that yield 35% 3-month progression-free survival rate (3MPFS) and (3) define the contribution of CBP501 to the effects of combination therapy.

Methods: CBP501 16 or 25 mg/m2 (CBP(16) or CBP(25)) was combined with 60 mg/m2 cisplatin (CDDP) and 240 mg nivolumab (nivo), administered at 3-week intervals. Patients were randomized 1:1:1:1 to (1) CBP(25)/CDDP/nivo, (2) CBP(16)/CDDP/nivo, (3) CBP(25)/CDDP and (4) CDDP/nivo, with randomization stratified by ECOG PS and liver metastases. A Fleming two-stage design was used, yielding a one-sided type I error rate of 2.5% and 80% power when the true 3MPFS is 35%.

Results: Among 36 patients, 3MPFS was 44.4% in arms 1 and 2, 11.1% in arm 3% and 33.3% in arm 4. Two patients achieved a partial response in arm 1 (ORR 22.2%; none in other arms). Median PFS and OS were 2.4, 2.1, 1.5 and 1.5 months and 6.3, 5.3, 3.7 and 4.9 months, respectively. Overall, all treatment combinations were well tolerated. Most treatment-related adverse events were grade 1-2.

Conclusions: The combination CBP(25)/(16)/CDDP/nivo demonstrated promising signs of efficacy and a manageable safety profile for the treatment of advanced PDAC.

Clinical trial registration: NCT04953962.

Keywords

Calmodulin inhibition; Immunochemotherapy; Pancreatic adenocarcinoma.

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