cabiralizumab (BMS-986227) / Ono Pharma, BMS, Amgen - LARVOL DELTA

Nivolumab Combined With BMS-986253 in HCC Patients (clinicaltrials.gov) - P2 | N=13 | Terminated | Sponsor: NYU Langone Health | N=23 ➔ 13 | Completed ➔ Terminated; Study was terminated early by the drug sponsor due to slow accrual and a change in the company's drug development priorities

Enrollment change • Trial termination • Hepatocellular Cancer • Oncology • Solid Tumor

Rationale and feasibility of a rapid integral biomarker program that informs immune-oncology clinical trials: the ADVISE trial. (PubMed, J Immunother Cancer) - P1 | "Actualization of a patient-specific I-O combination treatment selection strategy is feasible, however, determination of de novo integral biomarker thresholds of novel I-O targets to facilitate effective treatment of PD-1-refractory cancer remains fraught. These data emphasize the difficulty of integral biomarker development for I-O in translating from immunotherapy treatment-naïve biospecimens to the selection of patients in the PD-1-refractory state."

Biomarker • IO biomarker • Journal • Gastric Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer • CD8 • CSF1R • FOXP3 • IDO1 • LAG3 • PD-L1 • TNFA

Nivolumab Combined With BMS-986253 in HCC Patients (clinicaltrials.gov) - P2 | N=23 | Completed | Sponsor: NYU Langone Health | Active, not recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ Jan 2025

Trial completion • Trial completion date • Hepatocellular Cancer • Oncology • Solid Tumor

Nivolumab + Cabiralizumab + Gemcitabine in Patients With Stage IV Pancreatic Cancer (clinicaltrials.gov) - P2 | N=2 | Completed | Sponsor: Hitendra Patel | Suspended ➔ Completed | N=40 ➔ 2

Enrollment change • Trial completion • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

A CD8 T Cell Radiomics Score Correlates with Local Failure in Patients Undergoing Combined SBRT and Immune Checkpoint Inhibition in a Pooled Analysis of Three Phase I Trials (ASTRO 2024) - "ICI agents included pembrolizumab or nivolumab combined with either ipilimumab, cabiralizumab, or urelumab. Our results support the prognostic utility of this CD8 T cell RS in patients undergoing SBRT+ICI. Future work will investigate using the RS for treatment selection in patients with advanced solid tumors."

Checkpoint inhibition • IO biomarker • P1 data • Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8

Local and Marginal Failures in Spinal and Non-Spinal Osseous Metastases Receiving SBRT and Immunotherapy: A Secondary Analysis of Phase I Trials (ASTRO 2024) - "Materials/ Between 2016 and 2020, patients with widely metastatic solid malignancies were treated on three phase I trials (n = 213) combining multi-site SBRT with immunotherapy (regimens included pembrolizumab, ipilimumab with nivolumab, urelumab with nivolumab, or cabiralizumab with nivolumab; administered concurrently or sequentially). In widely metastatic patients receiving immunotherapy, the rate of local failure was low and marginal failures were not observed after SBRT to bone metastases, even with 0mm CTV expansions for non-spine lesions. Both histology and lesion location were associated with local failure. These findings inform adequate target delineation for future trials utilizing SBRT to non-spine and spine bone metastases."

P1 data • Oncology • Solid Tumor

Safety of combined ablative radiotherapy and immune checkpoint inhibitors in three phase I trials. (PubMed, Eur J Cancer) - "This analysis features the largest prospectively evaluated cohort of patients treated with combination ablative SBRT and ICI to date and provides context for future trial design. We conclude that multi-site SBRT and ICI can be safely co-administered when SBRT is delivered with prioritization of normal tissue constraints."

Checkpoint inhibition • Journal • P1 data • Oncology

APX005M With Nivolumab and Cabiralizumab in Advanced Melanoma, Non-small Cell Lung Cancer or Renal Cell Carcinoma (clinicaltrials.gov) - P1 | N=42 | Completed | Sponsor: Yale University | Active, not recruiting ➔ Completed | Trial completion date: Oct 2027 ➔ May 2024

Combination therapy • IO biomarker • Metastases • Trial completion • Trial completion date • Genito-urinary Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • BRAF • CD163 • CD40LG • CD8 • IFNG • IL10 • PD-L1

Nivolumab and the Antagonistic CSF-1R Monoclonal Antibody Cabiralizumab (BMS-986227) in Patients With Relapsed/Refractory Peripheral T Cell Lymphoma (clinicaltrials.gov) - P2 | N=4 | Completed | Sponsor: University of Michigan Rogel Cancer Center | Active, not recruiting ➔ Completed

Trial completion • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • TNFRSF8

A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better. (PubMed, Mol Cancer) - P1 | "Higher anti-CSF1R doses are inferior to lower doses in a preclinical model, inducing a suppressive macrophage population, and potentially explaining the disappointing results observed in patients. While it is impossible to directly infer human doses from murine studies, careful intra-species evaluation can provide important insight. Cabiralizumab dose optimization is necessary for this patient population with limited treatment options."

IO biomarker • Journal • Melanoma • Oncology • Solid Tumor • CD40

SAFETY, EFFICACY, AND PATIENT-REPORTED OUTCOMES WITH VIMSELTINIB IN PATIENTS WITH TENOSYNOVIAL GIANT CELL TUMOR WHO RECEIVED PRIOR ANTI–COLONY-STIMULATING FACTOR 1 THERAPY: ONGOING PHASE 2 UPDATE (CTOS 2023) - P1/2 | " Pts with TGCT not amenable to surgery who received prior anti-CSF1/CSF1R therapy (including pexidartinib, cabiralizumab, or vimseltinib) were enrolled and treated with vimseltinib 30 mg twice weekly (recommended phase 2 dose). Longer follow-up demonstrated that vimseltinib continued to be well tolerated with a manageable safety profile in pts with TGCT not amenable to surgery who received prior anti-CSF1/CSF1R therapy. Antitumor activity continued to improve in this pretreated population, with an increased ORR. At week 25, all responders experienced ≥30% reductions in worst and average pain."

P2 data • Patient reported outcomes • Giant Cell Tumor of Bone • Non-melanoma Skin Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • Tenosynovial Giant Cell Tumor • CSF1 • CSF1R

Predictors of Hepatotoxicity in Patients with Metastatic Solid Tumors Treated with Immune Checkpoint Inhibition (ICI) and Liver-Directed SBRT (ASTRO 2023) - "ICI agents included pembrolizumab alone or dual agent ICI with nivolumab and either cabiralizumab, urelumab, or ipilimumab. LM-SBRT did not significantly increase the risk for hepatotoxicity in patients receiving ICI when respecting the above dose constraints. Risk for hepatotoxicity appears to be driven by dual agent ICI and underlying liver disease. Abstract 215 - Table 1 HAE Grade All LM-SBRT NL-SBRT p 1 15% 20% 12% 0.4 2 9% 11% 8% 0.9 3 5% 6% 4% 0.8 4 1% 0% 1% –"

Checkpoint inhibition • Clinical • Metastases • Autoimmune Hepatitis • Fibrosis • Gastrointestinal Cancer • Hepatology • Immunology • Liver Cancer • Liver Failure • Oncology • Solid Tumor

Predictors of Hepatotoxicity in Patients with Metastatic Solid Tumors Treated with Immune Checkpoint Inhibition (ICI) and Liver-Directed SBRT. (PubMed, Int J Radiat Oncol Biol Phys) - "LM-SBRT did not significantly increase the risk for hepatotoxicity in patients receiving ICI when respecting the above dose constraints. Risk for hepatotoxicity appears to be driven by dual agent ICI and underlying liver disease."

Checkpoint inhibition • Journal • Metastases • Autoimmune Hepatitis • Fibrosis • Gastroenterology • Gastrointestinal Cancer • Hepatology • Immunology • Liver Cancer • Liver Failure • Oncology • Solid Tumor

A Study of Cabiralizumab Given With Nivolumab With and Without Chemotherapy in Patients With Advanced Pancreatic Cancer (clinicaltrials.gov) - P2 | N=206 | Completed | Sponsor: Bristol-Myers Squibb | Active, not recruiting ➔ Completed | Trial completion date: Oct 2023 ➔ Jun 2023 | Trial primary completion date: Oct 2023 ➔ Jun 2023

Combination therapy • Metastases • Trial completion • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Updates on the Treatment of Tenosynovial Giant Cell Tumor. (PubMed, Hematol Oncol Stem Cell Ther) - "Pexidartinib is the first CSF-1 receptor inhibitor approved for the treatment of TGCT. Here, we discuss various available treatment strategies and ongoing investigations and trials targeting diffuse TGCT, which include nilotinib, lacnotuzumab, cabiralizumab, vimseltinib, and emactuzumab."

Journal • Review • Giant Cell Tumor of Bone • Oncology • Tenosynovial Giant Cell Tumor

Nivolumab + Cabiralizumab + Gemcitabine in Patients With Stage IV Pancreatic Cancer Achieving Disease Control in Response to First-line Chemotherapy (GemCaN Trial). (clinicaltrials.gov) - P2 | N=40 | Suspended | Sponsor: Hitendra Patel | Trial completion date: Dec 2021 ➔ Dec 2023 | Trial primary completion date: Dec 2021 ➔ Dec 2023

Metastases • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better (AACR 2023) - "We previously conducted a phase 1 trial of cabiralizumab (anti-CSF1R) with sotigalimab (CD40 agonistic antibody) and nivolumab. Our study suggests that more anti-CSF1R might not be better. Further optimization of cabiralizumab dosing is necessary to evaluate the clinical potential in combination with anti-PD-1 and anti-CD40 in a difficult-to treat patient population whose therapeutic options are limited."

Melanoma • Oncology • Solid Tumor

Neoadjuvant Nivolumab and Chemotherapy in Patients With Localized Triple-negative Breast Cancer (clinicaltrials.gov) - P1/2 | N=15 | Active, not recruiting | Sponsor: Washington University School of Medicine | Recruiting ➔ Active, not recruiting | N=31 ➔ 15 | Trial completion date: Jun 2027 ➔ May 2026 | Trial primary completion date: Apr 2024 ➔ Mar 2023

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2

A randomized phase II study of cabiralizumab (cabira) + nivolumab (nivo) ± chemotherapy (chemo) in advanced pancreatic ductal adenocarcinoma (PDAC). (ASCO-GI 2019) - P1a/1b, P2; "... Pts aged ≥18 y with locally advanced/metastatic PDAC that progressed on/after first-line chemo (gemcitabine [gem] or 5-fluorouracil [5-FU] based) will be enrolled...Depending on prior chemo received, pts will be randomized to 1 of 4 arms (n≈40 each): cabira + nivo; cabira + nivo + gem/nab-paclitaxel; cabira + nivo + oxaliplatin/5-FU/leucovorin; or investigator’s choice of standard-of-care chemo...In a completed preliminary safety cohort, 12 pts were treated with cabira + nivo + chemo and monitored for 4 wk; competitive enrollment is open, with 32 pts enrolled. (NCT03336216, NCT02526017)"

Clinical • P2 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer

A randomized phase II study of cabiralizumab (cabira) + nivolumab (nivo) ± chemotherapy (chemo) in advanced pancreatic ductal adenocarcinoma (PDAC). (ASCO-GI 2019) - P1a/1b, P2; "... Pts aged ≥18 y with locally advanced/metastatic PDAC that progressed on/after first-line chemo (gemcitabine [gem] or 5-fluorouracil [5-FU] based) will be enrolled...Depending on prior chemo received, pts will be randomized to 1 of 4 arms (n≈40 each): cabira + nivo; cabira + nivo + gem/nab-paclitaxel; cabira + nivo + oxaliplatin/5-FU/leucovorin; or investigator’s choice of standard-of-care chemo...In a completed preliminary safety cohort, 12 pts were treated with cabira + nivo + chemo and monitored for 4 wk; competitive enrollment is open, with 32 pts enrolled. (NCT03336216, NCT02526017)"

Clinical • P2 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer

Pharmacodynamics (PD) and genomic profiling of pts treated with cabiralizumab (cabira) + nivolumab (NIVO) provide evidence of on-target tumor immune modulations and support future clinical applications. (ASCO 2018) - P1a/1b; "Orthogonal IHC and transcriptome-wide analyses demonstrated cabira-mediated CSF-1R blockade in the periphery and tumor microenvironment in pts with advanced cancer. Ongoing analyses include identification of transcriptomic signatures associated with response. These data support further clinical development of cabira + NIVO in multiple indications, including MSS pancreatic cancer"

Clinical • PD(L)-1 Biomarker • PK/PD data • Tumor mutational burden • Microsatellite Instability • Pancreatic Cancer

Phase Ib/II study to evaluate safety and tolerability of cabiralizumab in combination with nivolumab and neoadjuvant chemotherapy in patients with localized triple-negative breast cancer (SABCS 2022) - P1/2 | "Therefore, we examined the addition of cabiralizumab, a CSF1R inhibitor, to neoadjuvant paclitaxel, carboplatin, and nivolumab to assess the safety, tolerability, and changes in the tumor microenvironment (TME) in patients with early-stage TNBC. Between December 2020 and May 2022, we enrolled 12 patients to the safety lead-in, including 6 patients in each arm. 5 of 12 patients (41.7%) enrolled are underrepresented minorities, including 4 Black patients and 1 Hispanic patient. 2 of 6 patients in the nivolumab arm experienced grade 3 severe toxicity, including 1 patient who developed sepsis and 1 who developed peripheral neuropathy."

Clinical • Combination therapy • P1/2 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

C4-MOSART: Stereotactic Body Radiotherapy (SBRT) Plus Immunotherapy for Cancer (clinicaltrials.gov) - P1 | N=60 | Completed | Sponsor: University of Chicago | Active, not recruiting ➔ Completed

Immuno-oncology • Metastases • Trial completion • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

A phase I/II dose escalation and expansion study of cabiralizumab (cabira; FPA-008), an anti-CSF1R antibody, in tenosynovial giant cell tumor (TGCT, diffuse pigmented villonodular synovitis D-PVNS). (ASCO 2017) - P1/2; "The initial demonstration of objective and functional activity supports further development of cabiralizumab in pts with D-TGCT. Updated data from the ongoing Ph2 will be presented. NCT02471716."

Adverse events • P1/2 data • Biosimilar • Cardiovascular • Immunology • Oncology • Pain

Nivolumab and the Antagonistic CSF-1R Monoclonal Antibody Cabiralizumab (BMS-986227) in Patients With Relapsed/Refractory Peripheral T Cell Lymphoma (clinicaltrials.gov) - P2 | N=4 | Active, not recruiting | Sponsor: Ryan Wilcox | Trial completion date: Aug 2024 ➔ Jul 2023

Trial completion date • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • TNFRSF8