We further detail past and ongoing therapeutic efforts and trials addressing these axes in both PDAC and relevant non-PDAC settings via several small-molecule antagonists and monoclonal antibodies: BMS-813160, Maraviroc, Leronlimab, FLX475, PF-07054894, IDOR- 1117-2520, and CAP-100. Despite continuous advances in the field, the current body of evidence remains limited and presents significant research gaps in areas such as spatial profiling, stage-specific analyses, and general mechanistic validation in PDAC-specific settings. Addressing these shortcomings will be key to developing a more comprehensive knowledge of the field and improving future therapeutic strategies to overcome PDAC.

1 month ago

Review • Journal • IO biomarker

CCR4 (C-C Motif Chemokine Receptor 4) • CCL20 (C-C Motif Chemokine Ligand 20) • CCL19 (C-C Motif Chemokine Ligand 19) • CCR7 (Chemokine (C-C motif) receptor 7) • CCL2 (Chemokine (C-C motif) ligand 2) • CCR2 (C-C Motif Chemokine Receptor 2) • CCR6 (C-C Motif Chemokine Receptor 6)

tivumecirnon (FLX475) • Selzentry (maraviroc) • Vyrologix (leronlimab) • BMS-813160

2ms

Phase 1b/2 study of BMS-813160, a CCR2/5 dual antagonist, in combination with chemotherapy or nivolumab in patients with advanced pancreatic or colorectal cancer. (PubMed, J Immunother Cancer)

In 1L PDAC, BMS-813160 300 two times a day+gem/nabP±nivolumab demonstrated durable antitumor response and was well tolerated. BMS-813160 combination regimens were tolerable in other cohorts, but clinical efficacy was not demonstrated.

2 months ago

P1/2 data • Journal

CCR2 (C-C Motif Chemokine Receptor 2)

Opdivo (nivolumab) • gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • irinotecan • leucovorin calcium • BMS-813160

5ms

A Study of BMS-813160 in Combination With Chemotherapy or Nivolumab in Participants With Advanced Solid Tumors (clinicaltrials.gov)

P1/2, N=332, Completed, Bristol-Myers Squibb | Phase classification: P1b/2 --> P1/2

5 months ago

Phase classification

Opdivo (nivolumab) • gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • irinotecan • leucovorin calcium • BMS-813160

6ms

Trial of Neoadjuvant and Adjuvant Nivolumab and BMS-813160 With or Without GVAX for Locally Advanced Pancreatic Ductal Adenocarcinomas. (clinicaltrials.gov)

P1/2, N=46, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Sep 2024 --> Feb 2025 | Trial primary completion date: Sep 2024 --> Feb 2025

6 months ago

Trial completion date • Trial primary completion date

Opdivo (nivolumab) • BMS-813160 • GVAX Pancreas (allogeneic GM-CSF-secreting tumor cells)

1year

Neoadjuvant BMS-813160, nivolumab, gemcitabine and nab-paclitaxel for patients with pancreatic cancer. (PubMed, Clin Cancer Res)

Neoadjuvant BMS-813160/nivolumab/GnP was well tolerated and appears to achieve comparable ORR and resectability to historical data, however with prolonged PFS and OS in LA-PDAC patients, warranting a larger phase II study with a more efficacious CCR2-targeted therapeutic.

1 year ago

Journal • PD(L)-1 Biomarker

CCR2 (C-C Motif Chemokine Receptor 2)

Opdivo (nivolumab) • gemcitabine • albumin-bound paclitaxel • BMS-813160

1year

GCO 19-1754: Neoadjuvant Nivolumab with CCR2/5-inhibitor or Anti-IL-8) for Non-small Cell Lung Cancer (NSCLC) or Hepatocellular Carcinoma (HCC) (clinicaltrials.gov)

P2, N=48, Active, not recruiting, Icahn School of Medicine at Mount Sinai | Completed --> Active, not recruiting | Trial completion date: Nov 2023 --> Dec 2025 | Trial primary completion date: Nov 2023 --> Dec 2025

1 year ago

Enrollment closed • Trial completion date • Trial primary completion date

Opdivo (nivolumab) • BMS-813160 • BMS-986253

over1year

Trial of Neoadjuvant and Adjuvant Nivolumab and BMS-813160 With or Without GVAX for Locally Advanced Pancreatic Ductal Adenocarcinomas. (clinicaltrials.gov)

P1/2, N=46, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting --> Completed | N=30 --> 46 | Trial completion date: Dec 2024 --> Sep 2024 | Trial primary completion date: Dec 2024 --> Sep 2024

over 1 year ago

Trial completion • Enrollment change • Trial completion date • Trial primary completion date • Metastases

TNFRSF9 (TNF Receptor Superfamily Member 9)

Opdivo (nivolumab) • BMS-813160 • GVAX Pancreas (allogeneic GM-CSF-secreting tumor cells)

over1year

BMS-813160 With Nivolumab and Gemcitabine and Nab-paclitaxel in Borderline Resectable and Locally Advanced Pancreatic Ductal Adenocarcinoma (PDAC) (clinicaltrials.gov)

P1/2, N=40, Completed, Washington University School of Medicine | Active, not recruiting --> Completed

over 1 year ago

Trial completion

Opdivo (nivolumab) • gemcitabine • albumin-bound paclitaxel • BMS-813160

almost2years

GCO 19-1754: Neoadjuvant Nivolumab With CCR2/5-inhibitor or Anti-IL-8) for Non-small Cell Lung Cancer (NSCLC) or Hepatocellular Carcinoma (HCC) (clinicaltrials.gov)

P2, N=48, Completed, Icahn School of Medicine at Mount Sinai | N=36 --> 48 | Trial completion date: Sep 2024 --> Nov 2023 | Active, not recruiting --> Completed

almost 2 years ago

Trial completion • Enrollment change • Trial completion date

Opdivo (nivolumab) • BMS-813160 • BMS-986253

2years

Trial of Neoadjuvant and Adjuvant Nivolumab and BMS-813160 With or Without GVAX for Locally Advanced Pancreatic Ductal Adenocarcinomas. (clinicaltrials.gov)

P1/2, N=30, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

2 years ago

Trial completion date • Trial primary completion date • Metastases

TNFRSF9 (TNF Receptor Superfamily Member 9)

Opdivo (nivolumab) • BMS-813160 • GVAX Pancreas (allogeneic GM-CSF-secreting tumor cells)