1625P - Multicenter, randomized, parallel group, phase II study to establish the efficacy and safety of CBP501, cisplatin, and nivolumab for ≥ third-line treatment of patients with exocrine pancreatic cancer and WBC <10,000/mm3

Background

Metastatic pancreatic adenocarcinoma (PDAC) is an aggressive disease without third line standard-of-care treatment option. CBP501, a 12-amino acid G2 checkpoint abrogator and calmodulin-modulating peptide increases platinum influx into tumour cells, suppresses platinum-induced macrophage cytokine release and enhances anti-tumor activity with anti-programmed cell death-1 (anti-PD-1).

Methods

Patients with metastatic PDAC, who failed two lines of systemic therapy, with white blood cell count <10,000/mm³ were stratified by ECOG (0 vs 1) and liver metastasis (present vs absent) and randomized 1:1:1:1 to arm 1 - CBP501 25 mg/m² + cisplatin 60 mg/m² + nivolumab 240 mg; arm 2 - CBP501 16 mg/m² + cisplatin 60 mg/m² + nivolumab 240 mg; arm 3 - CBP501 25 mg/m² + cisplatin 60 mg/m²; or arm 4 - cisplatin 60 mg/m² + nivolumab 240 mg. Patients received 4 cycles of combination therapy then 6 cycles of nivolumab every 21 days if without disease progression (nivolumab arms only). The primary endpoint was 3-month progression-free survival rate (3M PFSR) in the ITT population. Secondary endpoints were safety, PFS, objective response rate (ORR) and overall survival (OS).

Results

As of October 17, 2022, efficacy was evaluable in 36 patients. 3M PFSR were 44%, 22%, 11% and 33% in arms 1, 2, 3 and 4, respectively. ORR were 22% in arm 1 (2 partial responses), 0% in arms 2, 3 and 4. Median PFS were 2.8, 2.1, 1.5 and 1.5 months, respectively. Median OS was not reached in arm 1 and 7.0, 2.7 and 3.8 months in arms 2, 3 and 4. Most common AEs were infusion-related reaction in 18/25 (72%; grade 1-2) during CBP501 infusion, and anemia in 2/33 (6%; both grade 3). SAEs occurred in 14/33 (42%); 13 SAEs were unrelated to CBP501. SAE acute renal failure (arm 3, after 1 cycle) was assessed as possibly related to CBP501 and definitely related to cisplatin.

Conclusions

Preliminary results indicate clinically meaningful improvement and tolerable safety of CBP501, cisplatin and nivolumab as 3rd line treatment for metastatic PDAC.

Clinical trial identification

NCT04953962.

Editorial acknowledgement

Legal entity responsible for the study

CanBas Co., Ltd.

Funding

CanBas Co., Ltd.

Disclosure

T. Enzler: Financial Interests, Personal, Funding, Research money for company trials: AstraZeneca Pharmaceuticals, Amgen, Taiho Oncology, NeoImmuneTech, Abbvie, Hosier Cancer Research Network, Exelixis, CanBas, Arcus Biosciences, Agenus, Tvardi, ECOG-ACRIN; Financial Interests, Institutional, Funding, Research money for company trials: BioMed Valley Discoveries. A. Nguyen: Financial Interests, Personal, Advisory Board, Speaker's bureau,: AstraZeneca Pharmaceuticals; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Advisory Board, Speaker's bureau, travel: BeiGene. V.J. Cline: Financial Interests, Personal, Leadership Role, Stocks: Texas Oncology Austin; Financial Interests, Personal, Principal Investigator, Texas Oncology-Austin 901 West: CanBas; Financial Interests, Personal, Invited Speaker, Multiple lunches, honoraria: Texas Oncology-Austin 901 West. A.S. Paulson: Financial Interests, Personal, Stocks/Shares: Actinum pharmaceuticals, Aptose Biosciences, Alexion Pharmaceuticals, Lynx Health, Stromatis Pharma; Financial Interests, Personal, Other, Honoraria: Cardinal Health; Financial Interests, Personal, Advisory Role: Amgen, Bristol Myers Squibb, Eisai, Ipsen, Advanced Accelerator Applications, Incyte, Exelixis, Pfizer, QED Therapeutics, Lilly, Mirati Therapeutics, Hutchinson MediPharma, Astellas Pharma, AADi, Stromatis Pharma, EMD Serono, AstraZeneca, Servier; Financial Interests, Personal, Speaker’s Bureau: Ideo Oncology; Financial Interests, Institutional, Research Grant: Ipsen, Bristol Myers Squibb, Exelixis, Hutchinson MediPharma, Taiho Pharmaceutical, Lilly, AstraZeneca, Incyte, Deciphera, GI Therapeutics, Zentalis, Tempus, Camurus, Relay Therapeutics, Nucana, Merk, Bayer, Seagen, Sotio, Innovative Cellular Therapeutics Co, Regenxbio, Gilead Sciences, Griststone Bio, BioNTech SE; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer, Camurus. W. Messersmith: Financial Interests, Personal and Institutional, Research Funding: CanBas Co., Ltd., Genentech, BeiGene, Pfizer, NGM Gossamer, ALX, Exelixis, EDDC/D3, Mirati; Financial Interests, Personal, Other, Data Safety Monitoring Committee: Amgen. J. Chaves: Financial Interests, Personal, Stocks/Shares: Johnson and Johnson; Financial Interests, Personal, Advisory Board: Janssen. E. Pierce: Financial Interests, Personal, Advisory Board, Honoraria, Speaker's Bureau: Janssen, Exelixis, Helsinn Therapeutics, Sanofi Genzyme; Financial Interests, Personal, Advisory Board, Honoraria: Seagen, Eisai; Financial Interests, Personal, Speaker’s Bureau, Honoraria: Merck. V. Sahai: Financial Interests, Institutional, Research Funding: Actuate Therapeutics, Agios, Bristol Myers Squibb, Celgene, Clovis, Cornerstone, Exelixis, FibroGen, Incyte, Ipsen, MedImmune, Relay, Repare, Syrios; Financial Interests, Institutional, Research Grant: NCI; Financial Interests, Personal, Other, Consultant: AstraZeneca, Autem, Cornerstone, Delcath Systems, GSK, Helsinn, Histosonics, Ipsen, Incyte, Kinnate, Lynx Group/Amplity, Servier, Taiho; Financial Interests, Personal and Institutional, Other, Provision of equipment/supplies: BeiGene, Cornerstone. D. Orr: Financial Interests, Personal, Stocks/Shares: Avalo Therapeutics; Financial Interests, Personal, Stocks/Shares, "Blind stock" portfolio: Northwestern Mutual. T. Kawabe: Financial Interests, Personal, Stocks/Shares, Leadership, patents/royalties, travel and accomodations,: CanBas Co., Ltd. All other authors have declared no conflicts of interest.