Study of CBP501/Cisplatin/Nivolumab Combinations in Advanced Pancreatic Cancer

NCT04953962 | Completed Phase 2 FDA Drug

• 1 other identifier: CBP21-01
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 20

Brief Summary

Multicenter, randomized, open-label, parallel group phase 2 study to assess the efficacy and tolerance of four combinations of CBP501, cisplatin, and nivolumab administered once every 21 days to patients with stage IV exocrine pancreatic cancer and WBC \< 10,000/mm3 at screening.

Conditions

Pancreatic Cancer Stage IV

Outcome Measures

Primary Outcomes (1)

• Three-month progression free survival rate (3M PFSR)

  Tumor assessment by RECIST v.1.1 criteria will be performed at screening, every 8 weeks starting after Cycle 1 Day 1, at the End-of-Treatment visit, and every 3 months after the End-of-Treatment visit until disease progression is observed.

  3 months after treatment

Secondary Outcomes (6)

• Safety profiles of the combinations of CBP501, cisplatin, and nivolumab administered once every 21 days

  One year

• Progression-free survival (PFS)

  one year

• Confirmed and timepoint objective response rates (cORR/ORR)

  one year

• Duration of responses (DoR)

  one year

• disease control rate (DCR: CR + PR + SD ≥12 weeks)

  one year

Study Arms (4)

Arm 1: CBP501 (25) + Cisplatin + Nivolumab

EXPERIMENTAL

CBP501 25mg/m2 and Cisplatin 60mg/m2 will be administered simultaneously. Nivolumab 240mg will be administered following the completion of CBP501 and cisplatin infusions.

Drug: CBP501 (25); Drug: Cisplatin; Drug: Nivolumab

Arm 2: CBP501 (16) + Cisplatin + Nivolumab

EXPERIMENTAL

CBP501 16mg/m2 and Cisplatin 60mg/m2 will be administered simultaneously. Nivolumab 240mg will be administered following the completion of CBP501 and cisplatin infusions.

Drug: CBP501 (16); Drug: Cisplatin; Drug: Nivolumab

Arm 3: CBP501 (25) + Cisplatin

EXPERIMENTAL

CBP501 25mg/m2 and Cisplatin 60mg/m2 will be administered simultaneously.

Drug: CBP501 (25); Drug: Cisplatin

Arm 4: Cisplatin + Nivolumab

EXPERIMENTAL

Cisplatin 60mg/m2 will be administered as infusion and then Nivolumab 240mg will be administered.

Drug: Cisplatin; Drug: Nivolumab

Interventions

CBP501 (16) DRUG

16 mg/m2

Also known as: CBP501

Arm 2: CBP501 (16) + Cisplatin + Nivolumab

CBP501 (25) DRUG

25 mg/m2

Also known as: CBP501

Arm 1: CBP501 (25) + Cisplatin + Nivolumab; Arm 3: CBP501 (25) + Cisplatin

Cisplatin DRUG

60mg/m2

Also known as: CDDP

Arm 1: CBP501 (25) + Cisplatin + Nivolumab; Arm 2: CBP501 (16) + Cisplatin + Nivolumab; Arm 3: CBP501 (25) + Cisplatin; Arm 4: Cisplatin + Nivolumab

Nivolumab DRUG

240 mg

Also known as: Opdivo

Arm 1: CBP501 (25) + Cisplatin + Nivolumab; Arm 2: CBP501 (16) + Cisplatin + Nivolumab; Arm 4: Cisplatin + Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent obtained prior to initiation of any study-specific procedures and treatment;
• Patients with pathologically confirmed stage IV exocrine pancreatic cancer who have received at least two lines of systemic therapy for metastatic disease. Up to 10 of prior lines of systemic therapy (including prior cisplatin), chemoradiotherapy, radiotherapy or investigational agents the patient has received are allowed in order to be eligible, as long as all eligibility criteria are met, with the exception that a patient must not have received more than two prior lines incorporating anti-PD-1, anti-PD-L1, or anti-CTLA-4 immune checkpoint blockade.
• Patients who have received prior anti-PD-1, anti-PD-L1, or anti-CTLA-4 immune checkpoint blockade therapy must have tolerated therapy with no evidence of grade 4 toxicity or an immune-related event (any grade) that required treatment discontinuation. Patients who experienced an endocrine related dysfunction are eligible, provided they are on stable hormone replacement therapy;
• Male or female patients aged ≥ 18 years at time of informed consent;
• ECOG Performance Status (PS) 0-1;
• Life expectancy \> 3 months;
• Previous anticancer treatment must be discontinued at least 3 weeks prior to the initiation of study treatment (with the exception of 6 weeks for mitomycin C; 6 weeks for anti-androgen therapy if discontinued prior to treatment initiation, and 8 weeks for bicalutamide);
• Adequate bone marrow reserve, cardiac, liver, renal and metabolic function:
• white blood cell count (WBC) \<10,000/mm3;
• absolute neutrophil count (ANC) ≥ 1,500/mm3;
• platelet count ≥ 100,000/mm3;
• hemoglobin ≥ 9 g/dL;
• creatinine phosphokinase isozymes CPK-MB and CPK-MM ≤ upper limit of normal (ULN);
• serum troponin T levels within normal limits;
• bilirubin ≤ 1.5 x ULN;

You may not qualify if:

• Radiation therapy to \>30% of bone marrow prior to study entry;
• Prior chemotherapy with nitrosoureas, prior mitomycin C cumulative dose ≥ 25 mg/m2, prior bone marrow transplant, or prior intensive chemotherapy with stem cell support;
• Presence of any serious concomitant systemic disorders incompatible with the study in the opinion of the investigator (e.g., uncontrolled congestive heart failure, active infection, etc.);
• Any previous history of another malignancy (other than cured basal cell or squamous cell carcinoma of the skin or cured in-situ carcinoma) within 5 years of study entry;
• Presence of any significant central nervous system (CNS) or psychiatric disorder(s) that would hamper the patient's compliance;
• Evidence of peripheral neuropathy grade ≥ 2;
• Treatment with any other investigational agent or participation in another clinical trial within 28 days prior to study entry;
• Pregnant or breast-feeding patients or any patient with child-bearing potential not using adequate contraception;
• Known HIV, HBV, or HCV infection (excluding cured HBV and/or cured HCV infection);
• Active CNS metastases; however, patients with CNS metastases will be eligible if they have been treated and are stable without symptoms for 4 weeks after completion of treatment, with image documentation required, and must be off steroids;
• Who require chronic systemic steroid therapy or on any other form of immunosuppressive medication;
• Has received a live-virus vaccination within 30 days of planned treatment start;
• With known risk factors for bowel perforation, i.e., history of diverticulitis, intra-abdominal abscess, intestinal obstruction, or abdominal carcinomatosis;
• Has an active autoimmune disease or a documented history of autoimmune disease;
• Has a history pneumonitis or interstitial lung disease.

Sponsors & Collaborators

• CanBas Co. Ltd.: lead

Study Sites (20)

Arizona Oncology Associates, PC-HOPE

Tucson, Arizona, 85704, United States

Location

Ochsner Clinic Foundation

Los Angeles, California, 70121, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Medical Oncology Hematology Consultants, PA

Newark, Delaware, 19713, United States

Location

Illinois Cancer Specialists

Arlington Heights, Illinois, 60005, United States

Location

University of Michigan hospital

Ann Arbor, Michigan, 48109, United States

Location

Minnesota oncology Hematology, P.A.

Minneapolis, Minnesota, 55404, United States

Location

James D Sanchez

Henderson, Nevada, 89052, United States

Location

Oncology Hematology Care, Inc.

Cincinnati, Ohio, 45245, United States

Location

Texas Oncology-Austin Midtown

Austin, Texas, 78705, United States

Location

Mary Crowley Medical Research Center

Dallas, Texas, 75230, United States

Location

Texas Oncology-Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Texas Oncology-McAllen South Second Street

McAllen, Texas, 78503, United States

Location

Texas Oncology- McKinney

McKinney, Texas, 75071, United States

Location

Texas Oncology-San Antonio Northeast

San Antonio, Texas, 78217, United States

Location

Baylor Scott & White Medical Center

Temple, Texas, 76508, United States

Location

Texas Oncology-Northeast Texas

Tyler, Texas, 75702, United States

Location

Virginia Cancer Specialists, PC

Arrington, Virginia, 22205, United States

Location

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

Location

Northwest Cancer Specialists, P.C.

Vancouver, Washington, 98684, United States

Location

Related Publications (7)

• Mine N, Yamamoto S, Kufe DW, Von Hoff DD, Kawabe T. Activation of Nrf2 pathways correlates with resistance of NSCLC cell lines to CBP501 in vitro. Mol Cancer Ther. 2014 Sep;13(9):2215-25. doi: 10.1158/1535-7163.MCT-13-0808. Epub 2014 Jul 22.

  PMID: 25053821 BACKGROUND

• Krug LM, Wozniak AJ, Kindler HL, Feld R, Koczywas M, Morero JL, Rodriguez CP, Ross HJ, Bauman JE, Orlov SV, Ruckdeschel JC, Mita AC, Fein L, He X, Hall R, Kawabe T, Sharma S. Randomized phase II trial of pemetrexed/cisplatin with or without CBP501 in patients with advanced malignant pleural mesothelioma. Lung Cancer. 2014 Sep;85(3):429-34. doi: 10.1016/j.lungcan.2014.06.008. Epub 2014 Jul 5.

  PMID: 25047675 BACKGROUND

• Matsumoto Y, Shindo Y, Takakusagi Y, Takakusagi K, Tsukuda S, Kusayanagi T, Sato H, Kawabe T, Sugawara F, Sakaguchi K. Screening of a library of T7 phage-displayed peptides identifies alphaC helix in 14-3-3 protein as a CBP501-binding site. Bioorg Med Chem. 2011 Dec 1;19(23):7049-56. doi: 10.1016/j.bmc.2011.10.004. Epub 2011 Oct 7.

  PMID: 22032894 BACKGROUND

• Mine N, Yamamoto S, Saito N, Yamazaki S, Suda C, Ishigaki M, Kufe DW, Von Hoff DD, Kawabe T. CBP501-calmodulin binding contributes to sensitizing tumor cells to cisplatin and bleomycin. Mol Cancer Ther. 2011 Oct;10(10):1929-38. doi: 10.1158/1535-7163.MCT-10-1139. Epub 2011 Aug 10.

  PMID: 21831962 BACKGROUND

• Shapiro GI, Tibes R, Gordon MS, Wong BY, Eder JP, Borad MJ, Mendelson DS, Vogelzang NJ, Bastos BR, Weiss GJ, Fernandez C, Sutherland W, Sato H, Pierceall WE, Weaver D, Slough S, Wasserman E, Kufe DW, Von Hoff D, Kawabe T, Sharma S. Phase I studies of CBP501, a G2 checkpoint abrogator, as monotherapy and in combination with cisplatin in patients with advanced solid tumors. Clin Cancer Res. 2011 May 15;17(10):3431-42. doi: 10.1158/1078-0432.CCR-10-2345. Epub 2011 Jan 10.

  PMID: 21220472 BACKGROUND

• Sha SK, Sato T, Kobayashi H, Ishigaki M, Yamamoto S, Sato H, Takada A, Nakajyo S, Mochizuki Y, Friedman JM, Cheng FC, Okura T, Kimura R, Kufe DW, Vonhoff DD, Kawabe T. Cell cycle phenotype-based optimization of G2-abrogating peptides yields CBP501 with a unique mechanism of action at the G2 checkpoint. Mol Cancer Ther. 2007 Jan;6(1):147-53. doi: 10.1158/1535-7163.MCT-06-0371.

  PMID: 17237275 BACKGROUND

• Enzler T, Nguyen A, Misleh J, Cline VJ, Johns M, Shumway N, Paulson S, Siegel R, Larson T, Messersmith W, Richards D, Chaves J, Pierce E, Zalupski M, Sahai V, Orr D, Ruste SA, Haun A, Kawabe T. 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. Epub 2024 Feb 22.

  PMID: 38422585 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Cdc25C phosphatase (211-221); Cisplatin; Nivolumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2021
• First Posted: July 8, 2021
• Study Start: December 18, 2021
• Primary Completion: April 14, 2023
• Study Completion: April 14, 2023
• Last Updated: August 15, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (20)