Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Melanoma

Carcinoma, Renal Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Nivolumab

Immunoglobulins

Immunoglobulin G

Immunoglobulins, Intravenous

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Cabiralizumab 4mg/kg plus APX005M 0.03 mg/kg administered in 14 day cycles.

Nivolumab 240 mg plus Cabiralizumab 4mg/kg plus APX005M 0.03 mg/kg administered in 14 day cycles.

Cabiralizumab 4mg/kg plus APX005M 0.1 mg/kg administered in 14 day cycles.

Nivolumab 240 mg plus Cabiralizumab 4mg/kg plus APX005M 0.1 mg/kg administered in 14 day cycles.

Cabiralizumab 4mg/kg plus APX005M 0.3 mg/kg administered in 14 day cycles.

Nivolumab 240 mg plus Cabiralizumab 4mg/kg plus APX005M 0.3 mg/kg administered in 14 day cycles.

Patients will be treated at the estimated APX005M RP2D in combination with nivolumab 240 mg IV and cabiralizumab 4 mg/kg on day 1 of each 14-day cycle.

APX005M is a humanized Immunoglobulin G (IgG) 1 agonistic monoclonal antibody that binds cluster of differentiation (CD) 40. APX005M is administered by intravenous infusion.

APX005M

Cabiralizumab is a humanized Immunoglobulin G (IgG) 4 monoclonal antibody directed against Colony stimulating factor 1 receptor (CSF1R). Cabiralizumab is administered by intravenous infusion.

Cabiralizumab

Nivolumab is a humanized IgG4 monoclonal antibody directed against programmed cell death 1 (PD-1). Nivolumab is administered by intravenous infusion.

Harriet Kluger, MD

This trial is a phase 1/1b study to evaluate the safety, efficacy, and tolerability of APX005M in combination with nivolumab and cabiralizumab.

The phase 1 dose escalation portion of the study will enroll patients with advanced solid tumors melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) in 6 cohorts to determine the recommended phase II dose (RP2D) of APX005M.

The phase 1b dose expansion portion will study the triple drug combination separately in the three disease cohorts: melanoma, NSCLC, and RCC.

APX005M With Nivolumab and Cabiralizumab in Advanced Melanoma, Non-small Cell Lung Cancer or Renal Cell Carcinoma

A Phase I/Ib Study of APX005M in Combination With Nivolumab and Cabiralizumab in Patients With Advanced Melanoma, Non-small Cell Lung Cancer or Renal Cell Carcinoma Whose Disease Has Progressed on Anti-PD- 1/PD-L1 Therapy

This outcome will be assessed by blood collection.

This outcome will be assessed with tissue biopsies.

This outcome will be assessed via blood collection.

PFS will be determined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria v. 1.1.

OS will be ascertained by review of the National Death Index, medical records and follow-up phone calls.

AEs and SAEs will be examined with (National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 4.03.

This 5-point scale ranges from full functioning (0) to dead (5)

ORR will be determined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria v. 1.1. The RECIST categories used for the target lesion are complete response (CR), partial response (PR), stable disease (NR/SD), and progressive disease (PD).

Bristol-Myers Squibb

Apexigen America, Inc.

National Cancer Institute (NCI)

Yale University

Cabiralizumab 4mg/kg plus APX005M 0.03 mg/kg administered in 14 day cycles.

APX005M: APX005M is a humanized Immunoglobulin G (IgG) 1 agonistic monoclonal antibody that binds cluster of differentiation (CD) 40. APX005M is administered by intravenous infusion.

Cabiralizumab: Cabiralizumab is a humanized Immunoglobulin G (IgG) 4 monoclonal antibody directed against Colony stimulating factor 1 receptor (CSF1R). Cabiralizumab is administered by intravenous infusion.

Cohort 1 Advanced Solid Tumors

Nivolumab 240 mg plus Cabiralizumab 4mg/kg plus APX005M 0.03 mg/kg administered in 14 day cycles.

APX005M: APX005M is a humanized Immunoglobulin G (IgG) 1 agonistic monoclonal antibody that binds cluster of differentiation (CD) 40. APX005M is administered by intravenous infusion.

Cabiralizumab: Cabiralizumab is a humanized Immunoglobulin G (IgG) 4 monoclonal antibody directed against Colony stimulating factor 1 receptor (CSF1R). Cabiralizumab is administered by intravenous infusion.

Nivolumab: Nivolumab is a humanized IgG4 monoclonal antibody directed against programmed cell death 1 (PD-1). Nivolumab is administered by intravenous infusion.

Cohort 2 Advanced Solid Tumors

Cabiralizumab 4mg/kg plus APX005M 0.1 mg/kg administered in 14 day cycles.

APX005M: APX005M is a humanized Immunoglobulin G (IgG) 1 agonistic monoclonal antibody that binds cluster of differentiation (CD) 40. APX005M is administered by intravenous infusion.

Cabiralizumab: Cabiralizumab is a humanized Immunoglobulin G (IgG) 4 monoclonal antibody directed against Colony stimulating factor 1 receptor (CSF1R). Cabiralizumab is administered by intravenous infusion.

Cohort 3 Advanced Solid Tumors

Nivolumab 240 mg plus Cabiralizumab 4mg/kg plus APX005M 0.1 mg/kg administered in 14 day cycles.

APX005M: APX005M is a humanized Immunoglobulin G (IgG) 1 agonistic monoclonal antibody that binds cluster of differentiation (CD) 40. APX005M is administered by intravenous infusion.

Cabiralizumab: Cabiralizumab is a humanized Immunoglobulin G (IgG) 4 monoclonal antibody directed against Colony stimulating factor 1 receptor (CSF1R). Cabiralizumab is administered by intravenous infusion.

Nivolumab: Nivolumab is a humanized IgG4 monoclonal antibody directed against programmed cell death 1 (PD-1). Nivolumab is administered by intravenous infusion.

Cohort 4 Advanced Solid Tumors

Cabiralizumab 4mg/kg plus APX005M 0.3 mg/kg administered in 14 day cycles.

APX005M: APX005M is a humanized Immunoglobulin G (IgG) 1 agonistic monoclonal antibody that binds cluster of differentiation (CD) 40. APX005M is administered by intravenous infusion.

Cabiralizumab: Cabiralizumab is a humanized Immunoglobulin G (IgG) 4 monoclonal antibody directed against Colony stimulating factor 1 receptor (CSF1R). Cabiralizumab is administered by intravenous infusion.

Cohort 5 Advanced Solid Tumors

Nivolumab 240 mg plus Cabiralizumab 4mg/kg plus APX005M 0.3 mg/kg administered in 14 day cycles.

APX005M: APX005M is a humanized Immunoglobulin G (IgG) 1 agonistic monoclonal antibody that binds cluster of differentiation (CD) 40. APX005M is administered by intravenous infusion.

Cabiralizumab: Cabiralizumab is a humanized Immunoglobulin G (IgG) 4 monoclonal antibody directed against Colony stimulating factor 1 receptor (CSF1R). Cabiralizumab is administered by intravenous infusion.

Nivolumab: Nivolumab is a humanized IgG4 monoclonal antibody directed against programmed cell death 1 (PD-1). Nivolumab is administered by intravenous infusion.

Cohort 6 Advanced Solid Tumors

Patients will be treated at the estimated APX005M RP2D in combination with nivolumab 240 mg IV and cabiralizumab 4 mg/kg on day 1 of each 14-day cycle.

APX005M: APX005M is a humanized Immunoglobulin G (IgG) 1 agonistic monoclonal antibody that binds cluster of differentiation (CD) 40. APX005M is administered by intravenous infusion.

Cabiralizumab: Cabiralizumab is a humanized Immunoglobulin G (IgG) 4 monoclonal antibody directed against Colony stimulating factor 1 receptor (CSF1R). Cabiralizumab is administered by intravenous infusion.

Nivolumab: Nivolumab is a humanized IgG4 monoclonal antibody directed against programmed cell death 1 (PD-1). Nivolumab is administered by intravenous infusion.

Cohort 7 Advanced Melanoma

Patients will be treated at the estimated APX005M RP2D in combination with nivolumab 240 mg IV and cabiralizumab 4 mg/kg on day 1 of each 14-day cycle.

APX005M: APX005M is a humanized Immunoglobulin G (IgG) 1 agonistic monoclonal antibody that binds cluster of differentiation (CD) 40. APX005M is administered by intravenous infusion.

Cabiralizumab: Cabiralizumab is a humanized Immunoglobulin G (IgG) 4 monoclonal antibody directed against Colony stimulating factor 1 receptor (CSF1R). Cabiralizumab is administered by intravenous infusion.

Cohort 8 NSCLC

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

ECOG PS, Eastern Cooperative Oncology Group performance status is a scale that measures one's level of functioning in terms of ability to care for oneself, daily activity, and physical ability (walking, working, etc.) with a range of 0 to 5. A score of 0 indicates performance without restriction whereas a score of 5 indicates death (a higher score indicates worse functioning).

ECOG PS

Cancer Type

Experienced any SAE

Experienced any AE

Safety and Tolerability Measured by Assessing Serious Adverse Events (SAEs)and Adverse Events (AEs)

Safety and Tolerability Measured by Eastern Cooperative Oncology Group(ECOG) Performance Status

Only participants that completed at least 1 follow up assessment.

Efficacy Measured by Objective Response Rate (ORR)

Pharmacokinetics (PK) of APX005M Assessed by Area Under the Curve (AUC).

Pharmacokinetics (PK) of APX005M Assessed by Minimum Blood Plasma Concentration (Cmin).

Pharmacokinetics (PK) of APX005M Assessed by Clearance (CL).

Pharmacokinetics (PK) of APX005M Assessed by Volume of Distribution (Vss)

Pharmacokinetics (PK) of APX005M Assessed by Peak Plasma Concentration (Cmax).

Tissue-based Pharmacodynamics (PD) of APX005M, in Combination With Nivolumab and Cabiralizumab Assessed by CD8+ T Cells .

Tissue-based Pharmacodynamics (PD) of APX005M, in Combination With Nivolumab and Cabiralizumab Assessed by CD163+ Macrophages .

Blood-based Pharmacodynamics (PD) of APX005M, in Combination With Nivolumab and Cabiralizumab Assessed by Circulating CD163+ Macrophages .

Blood-based Pharmacodynamics (PD) of APX005M, in Combination With Nivolumab and Cabiralizumab Assessed by Circulating CD8+ T Cells.

Cytokine-based Pharmacodynamic (PD) Biomarkers of APX005M, in Combination With Nivolumab and Cabiralizumab Assessed by CD40L Levels.

Cytokine-based Pharmacodynamic (PD) Biomarkers of APX005M, in Combination With Nivolumab and Cabiralizumab Assessed by IL-10 Levels.

Cytokine-based Pharmacodynamic (PD) Biomarkers of APX005M, in Combination With Nivolumab and Cabiralizumab Assessed by Interferon-gamma Levels .

Efficacy Measured by Progression-free Survival (PFS)

Efficacy Measured by Overall Survival (OS)

Patients will be treated at the estimated APX005M RP2D in combination with nivolumab 240 mg IV and cabiralizumab 4 mg/kg on day 1 of each 14-day cycle.

APX005M: APX005M is a humanized Immunoglobulin G (IgG) 1 agonistic monoclonal antibody that binds cluster of differentiation (CD) 40. APX005M is administered by intravenous infusion.

THIS STUDY ARM/COHORT WAS NEVER ACTIVATED DURING THE STUDY.

Cabiralizumab: Cabiralizumab is a humanized Immunoglobulin G (IgG) 4 monoclonal antibody directed against Colony stimulating factor 1 receptor (CSF1R). Cabiralizumab is administered by intravenous infusion.

Nivolumab: Nivolumab is a humanized IgG4 monoclonal antibody directed against programmed cell death 1 (PD-1). Nivolumab is administered by intravenous infusion.

Cohort 9 RCC

Overall Study

Immunomodulating Agents

Ipilimumab

Relatlimab

Linrodostat

Enzyme Inhibitors

Combination therapy determined by biomarker assessment

IDO1 Inhibitor

Radiation Therapy

The purpose of this study is to evaluate the treatment of solid tumors with various immunotherapy combinations. The treatment will be determined based upon a broad biomarker assessment.

An Adaptive Study to Match Patients With Solid Tumors to Various Immunotherapy Combinations Based Upon a Broad Biomarker Assessment

ADaptiVe Biomarker Trial That InformS Evolution of Therapy

An adequate quality tumor biopsy providing sufficient information prior to choosing a combination immunotherapy/Stereotactic Body Radiation Therapy (SBRT)

Any laboratory test result that is clinically significant or meets the definition of an SAE, requires the participant to have study treatment discontinued, or receive specific corrective therapy

Number of Adverse Events leadind to discontinutaion

Symptoms and General Pathology

Neoplasm Metastasis

Patients will receive stereotactic body radiation therapy (SBRT) in combination with nivolumab and urelumab.

Patients will receive stereotactic body radiation therapy (SBRT) in combination with nivolumab and cabiralizumab .

Nivolumab 240 mg given by intravenous infusion every 2 weeks

Cabiralizumab 4 mg/kg given by intravenous infusion every 2 weeks

Urelumab 8 mg given by intravenous infusion every 4 weeks

Urelumab

Radiation to metastatic lesion(s) given at assigned dose levels based on lesion location and dose level being tested at time of enrollment. Doses range from 30 - 50 Gy.

Stereotactic Body Radiation Therapy

Jason Luke, MD

Study to determine the best dose of stereotactic body radiation therapy (SBRT) to be administered in combination with immunotherapy drugs including urelumab, cabiralizumab and nivolumab .

Patients will be enrolled in parallel based on physician preference and slot availability.

Stereotactic Body Radiotherapy (SBRT) Plus Immunotherapy for Cancer

Platform Phase 1 Study Investigating the Safety of Stereotactic Body Radiotherapy (SBRT) With Immuno-oncology Agents for the Treatment of Multiple Metastases in Advanced Solid Tumors

Dose of stereotactic body radiation therapy (SBRT) that can safety be given with immunotherapy.

Rate of side effects seen in study participants.

Rate of long term (occurring 6 month or more after treatment) side effects seen in study participants.

Number of participants that do not have disease worsening.

Rate of disease control (tumor shrinkage) of radiation treated lesions.

University of Chicago

Blood and Lymph Conditions

Immune System Diseases

Lymphoma

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Peripheral T-cell Lymphoma

Nivolumab 240mg IV + Cabiralizumab 4mg/kg on day 1 of every 14 day cycle.

Nivolumab is a human monoclonal antibody (HuMAb; immunoglobulin G4 \[IgG4\]-S228P) that targets the programmed death-1 (PD-1) cluster of differentiation 279 (CD279) cell surface membrane receptor. PD-1 is a negative regulatory molecule expressed by activated T and B lymphocytes.1 Binding of PD-1 to its ligands, programmed death-ligands 1 (PD-L1) and 2 (PD-L2), results in the down-regulation of lymphocyte activation. Inhibition of the interaction between PD-1 and its ligands promotes immune responses and antigen-specific T-cell responses to both foreign antigens as well as self-antigens. Nivolumab will be delivered intravenously at a fixed dose of 240 mg on day 1 of 14 day cycles.

Cabiralizumab is a recombinant, humanized Immunoglobulin G4 (IgG4) monoclonal antibody that binds to human colony stimulating factor 1 receptor (CSF1R; c-fms). Cabiralizumab will be delivered intravenously at a dosage of 4 mg/kg on day 1 of 14 day cycles.

cabiralizumab

Ryan Wilcox, MD, PhD

A multicenter trial evaluating the combination of nivolumab and the antagonistic CSF-1R monoclonal antibody cabiralizumab (BMS-986227) in patients with relapsed/refractory peripheral T cell lymphoma

Enrollment to this study was discontinued after four subjects due to industry-related changes to the Cabiralizumab program.

Nivolumab and the Antagonistic CSF-1R Monoclonal Antibody Cabiralizumab (BMS-986227) in Patients With Relapsed/Refractory Peripheral T Cell Lymphoma

Overall Response Rate (CR + PR) as determined by LYRIC (LYmphoma Response to Immunomodulatory therapy Criteria), at four months (shown as number of participants with CR or PR at 4 months).

LYRIC: An adaptation of the Lugano classification developed because discriminating true progressive disease from pseudoprogression in lymphoma patients receiving immunomodulatory agents is challenging. To address this challenge, the LYRIC criteria incorporated the response category of "indeterminate response" (IR).

* IR(1): ≥ 50% increase in overall tumor burden (sum of the product of the perpendicular diameters (SPD) of up to 6 target measurable nodes and extranodal sites) occurred in the 1st 12 weeks of therapy and without clinical deterioration
* IR(2): new lesions or ≥ 50% increase of existing lesion(s) without a ≥ 50% increase of overall tumor burden at any time during treatment.
* IR(3): increased FDG uptake of 1or more lesions without any increase in size or number of those lesions.

Complete response rate, as determined by LYRIC criteria, at four months (reported as number of participants with CR at 4 months).

LYRIC: An adaptation of the Lugano classification developed because discriminating true progressive disease from pseudoprogression in lymphoma patients receiving immunomodulatory agents is challenging. To address this challenge, the LYRIC criteria incorporated the response category of "indeterminate response" (IR).

* IR(1): ≥ 50% increase in overall tumor burden (sum of the product of the perpendicular diameters (SPD) of up to 6 target measurable nodes and extranodal sites) occurred in the 1st 12 weeks of therapy and without clinical deterioration
* IR(2): new lesions or ≥ 50% increase of existing lesion(s) without a ≥ 50% increase of overall tumor burden at any time during treatment.
* IR(3): increased FDG uptake of 1or more lesions without any increase in size or number of those lesions.

Overall response (CR + PR), as determined by LUGANO 2014 criteria (reported as number of participants with a CR or PR at 4 months).

The Lugano classification is utilized for both lymphoma staging and response assessment and incorporates PET-CT imaging. Responses are described as either partial or complete, with a complete response requiring disappearance of metabolically active sites of disease.

Complete Response Rate, as determined by LUGANO 2014 criteria, at (reported as number of participants with a CR at 4 months).

The Lugano classification is utilized for both lymphoma staging and response assessment and incorporates PET-CT imaging. A complete response requires disappearance of metabolically active sites of disease.

Progression-Free Survival will be measured from date of enrollment until the criteria for disease progression (PD) is met or death occurs. Subjects who have not progressed will be right-censored at the date of the last disease evaluation.

The proportion of all subjects with stable disease (SD) for 8 weeks, PR, or CR.

Duration of Response measured from the time that measurement criteria are met for CR or PR (whichever status is recorded first) until the date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since treatment started).

Time to next treatment (TNT) is defined as the time from the date of enrollment to the institution of next treatment.

Assess and summarize adverse events (AEs) using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.

University of Michigan Rogel Cancer Center

An AE is any untoward medical occurrence whether or not related to the study drug that appears to change in intensity during the course of the study.

Abnormal laboratory values or diagnostic test results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests Hospitalization for elective surgery or routine clinical procedures that are not the result of an AE (e.g.,surgical insertion of central line) should not be recorded as an AE.

Nivolumab 240mg IV + Cabiralizumab 4mg/kg on day 1 of every 14 day cycle.

Nivolumab is a human monoclonal antibody (HuMAb; immunoglobulin G4 \[IgG4\]-S228P) that targets the programmed death-1 (PD-1) cluster of differentiation 279 (CD279) cell surface membrane receptor. PD-1 is a negative regulatory molecule expressed by activated T and B lymphocytes.1 Binding of PD-1 to its ligands, programmed death-ligands 1 (PD-L1) and 2 (PD-L2), results in the down-regulation of lymphocyte activation. Inhibition of the interaction between PD-1 and its ligands promotes immune responses and antigen-specific T-cell responses to both foreign antigens as well as self-antigens.

Cabiralizumab is a recombinant, humanized Immunoglobulin G4 (IgG4) monoclonal antibody that binds to human colony stimulating factor 1 receptor (CSF1R; c-fms).

Nivolumab + Cabiralizumab

Ethnicity (NIH/OMB)

All subject consented, confirmed to be eligible, and registered to the trial.

Adelai Neal

All subjects with measurable disease who received at least one cycle of treatment and had disease re-evaluated.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
APX005M With Nivolumab and Cabiralizumab in Advanced Melanoma, Non-small Cell Lung Cancer or Renal Cell Carcinoma	NCT03502330	Advanced Melano... Non-small Cell ... Renal Cell Carc...	APX005M Cabiralizumab Nivolumab	18 Years -	Yale University
An Adaptive Study to Match Patients With Solid Tumors to Various Immunotherapy Combinations Based Upon a Broad Biomarker Assessment	NCT03335540	Advanced Cancer	Nivolumab Relatlimab Cabiralizumab Ipilimumab IDO1 Inhibitor Radiation Thera...	18 Years -	Bristol-Myers Squibb
Stereotactic Body Radiotherapy (SBRT) Plus Immunotherapy for Cancer	NCT03431948	Cancer	Nivolumab Cabiralizumab Urelumab Stereotactic Bo...	18 Years -	University of Chicago
Nivolumab and the Antagonistic CSF-1R Monoclonal Antibody Cabiralizumab (BMS-986227) in Patients With Relapsed/Refractory Peripheral T Cell Lymphoma	NCT03927105	Peripheral T Ce...	Nivolumab cabiralizumab	18 Years -	University of Michigan Rogel Cancer Center
Neoadjuvant Nivolumab and Chemotherapy in Patients With Localized Triple-negative Breast Cancer	NCT04331067	Triple Negative...	Paclitaxel Carboplatin Nivolumab Cabiralizumab Tumor biopsy Bone marrow Blood draw	18 Years -	Washington University School of Medicine
An Adaptive Study to Match Patients With Solid Tumors to Various Immunotherapy Combinations Based Upon a Broad Biomarker Assessment	NCT03335540	Advanced Cancer	Nivolumab Relatlimab Cabiralizumab Ipilimumab IDO1 Inhibitor Radiation Thera...	18 Years -	Bristol-Myers Squibb
Safety and Tolerability Study of Nivolumab and Cabiralizumab for Resectable Biliary Tract Cancer	NCT03768531	Resectable Bili...	Nivolumab Cabrilizumab	18 Years - 100 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Spots Global Cancer Trial Database for cabiralizumab