Symptoms and General Pathology

All Conditions

Recurrence

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Mitoguazone

Tubulin Modulators

Antimitotic Agents

Patients receive axatilimab IV over 30 minutes on day -8, prior to cycle 1. Beginning in cycle 1 day 1, patients receive axatilimab IV over 30 minutes on days 8 and 21 of each cycle, retifanlimab IV over 30-60 minutes on day 1 of each cycle, and paclitaxel IV over 60 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor biopsy, CT scan, and blood sample collection at screening and on study and may undergo MRI and/or PET scan at screening and on study.

Axatilimab

Biopsy

Biospecimen Collection

Computed Tomography

Magnetic Resonance Imaging

Positron Emission Tomography

Retifanlimab

Shivaani Kummar

This phase I/II trial tests the safety, side effects, and effectiveness of axatilimab in combination with retifanlimab and paclitaxel for the treatment of patients with a solid tumor that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Axatilimab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Immunotherapy with monoclonal antibodies, such as retifanlimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Giving axatilimab in combination with retifanlimab and paclitaxel may be safe, tolerable and/or effective in treating patients with advanced or metastatic solid tumors.

PRIMARY OBJECTIVES:

I. Phase Ib: Determine the safety and tolerability of the combination of axatilimab, retifanlimab, and paclitaxel in patients with advanced solid tumors.

II. Phase II: Determine the efficacy of the combination of axatilimab, retifanlimab, and paclitaxel in patients with advanced solid tumors.

SECONDARY OBJECTIVES:

I. Determine the safety and tolerability of the combination of axatilimab, retifanlimab, and paclitaxel in patients with advanced solid tumors treated in phase II.

II. Explore treatment related changes in the tumor microenvironment (TME) following treatment with the combination of axatilimab, retifanlimab, and paclitaxel in advanced solid tumors.

III. Assess predictive biomarkers of response in peripheral blood.

OUTLINE:

Patients receive axatilimab intravenously (IV) over 30 minutes on day -8, prior to cycle 1. Beginning in cycle 1 day 1, patients receive axatilimab IV over 30 minutes on days 8 and 21 of each cycle, retifanlimab IV over 30-60 minutes on day 1 of each cycle, and paclitaxel IV over 60 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor biopsy, computed tomography (CT) scan, and blood sample collection at screening and on study and may undergo magnetic resonance imaging (MRI) and/or positron emission tomography (PET) scan at screening and on study.

After completion of study treatment, patients are followed up at 30 and 90 days.

Axatilimab in Combination With Retifanlimab and Paclitaxel for the Treatment of Patients With Advanced or Metastatic Solid Tumors

A Phase Ib/II Study of Axatilimab in Combination With Retifanlimab and Paclitaxel for the Treatment of Patients With Advanced Solid Tumors

Will be coded by system organ class, MedDRA preferred term, and severity grade using Common Terminology Criteria for Adverse Events (version 5.0).

Defined as percentage of participants with complete response or partial response confirmed by scans at least 4 weeks apart, or stable disease for \> 4 months. Will be reported with exact 95% confidence interval.

Will be categorized and tabulated for reporting. The analyses for reporting may include descriptive statistical analyses of the overall set of phase II adverse events.

Will be characterized in peripheral blood using flow cytometry (FC) and candidate protein biomarkers will be identified in tumor tissue using multiplexed immunohistochemistry. Changes in immune cell composition and functionality at the biopsy during cycle 2 will be assessed by paired t-test.

To assess predictive biomarkers of response in peripheral blood, changes in immune cell populations in peripheral blood, including reduced presence of CD14dimCD16+ monocytes and increased presence of CD8+ T effector memory subsets, at the end of the study between responders and non-responders will be assessed using repeated measures of analysis of covariance over time to accommodate a longitudinal nature of peripheral blood draws for flow cytometry.

Oregon Health and Science University

Incyte Corporation

OHSU Knight Cancer Institute

Principal Investigator

Neoplasms

Neoplasm Metastasis

Neoplastic Processes

Durvalumab

Antineoplastic Agents, Immunological

Three (3) patients receive starting dose of 1 mg/kg of axatilimab and are followed for possible DLTs. If one DLT is observed in 1 of 3 patients, an additional 3 patients will be enrolled at this dose level. If no DLTs are noted in any of the 3 patients, next dosing arm will commence following review by Scientific Review Committee.

Three (3) patients receive next higher dose of 3 mg/kg of axatilimab and are followed for possible DLTs. If one DLT is observed in 1 of 3 patients, an additional 3 patients will be enrolled at this dose level. If no DLTs are noted in any of the 3 patients, next dosing arm will commence following review by Scientific Review Committee.

Three (3) patients receive next higher dose of 6 mg/kg of axatilimab and are followed for possible DLTs. If one DLT is observed in 1 of 3 patients, an additional 3 patients will be enrolled at this dose level. If no DLTs are noted in any of the 3 patients, next dosing arm will commence following review by Scientific Review Committee.

Three (3) patients receive next higher dose of 10 mg/kg of axatilimab and are followed for possible DLTs. If one DLT is observed in 1 of 3 patients, an additional 3 patients will be enrolled at this dose level. If no DLTs are noted in any of the 3 patients, next dosing arm will commence following review by Scientific Review Committee.

Three (3) patients receive starting dose of 1 mg/kg of axatilimab every two weeks and 1500 mg durvalumab every four weeks and are followed for possible DLTs. If one DLT is observed in 1 of 3 patients, an additional 3 patients will be enrolled at this dose level. If no DLTs are noted in any of the 3 patients, next dosing arm will commence following review by Scientific Review Committee. If 1 DLT is observed in 1 of 3 patients, then 3 additional patients will be treated at the 1 mg/kg axatilimab dose level; if none of the 3 additional patients experience a DLT (i.e. 1 of 6), the dose will be escalated to an intermediate dose of 2 mg/kg. Escalation from 2 mg/kg to 3 mg/kg will follow the general dose escalation rules described above for both study phases.

Three (3) patients receive next higher dose of 3 mg/kg of axatilimab every two weeks and 1500 mg durvalumab every four weeks and are followed for possible DLTs. For cohorts with doses ≥3 mg/kg, a sentinel recruitment approach will be utilized. Initially 1 patient in each cohort will be treated with the combination therapy and safety will be evaluated by SRC at Cycle 1, Day 8; if no safety concerns are identified, the next 2 patients can be treated in that cohort. If one DLT is observed in 1 of 3 patients, an additional 3 patients will be enrolled at this dose level. If no DLTs are noted in any of the 3 patients, next dosing arm will commence following review by Scientific Review Committee.

Three (3) patients receive next higher dose of 6 mg/kg of axatilimab every two weeks and 1500 mg durvalumab every four weeks and are followed for possible DLTs. For cohorts with doses ≥3 mg/kg, a sentinel recruitment approach will be utilized. Initially 1 patient in each cohort will be treated with the combination therapy and safety will be evaluated by SRC at Cycle 1, Day 8; if no safety concerns are identified, the next 2 patients can be treated in that cohort. If one DLT is observed in 1 of 3 patients, an additional 3 patients will be enrolled at this dose level. If no DLTs are noted in any of the 3 patients, next dosing arm will commence following review by Scientific Review Committee.

Humanized IgG4 mAb that blocks colony stimulating factor 1 receptor (CSF-1R)

Durvalumab (MEDI4736) is a humanized IgG1 kappa mAb that blocks the interaction of PD-L1 with PD-1 CD80 (B7.1) molecules

Kate Madigan, MD

A Phase 1 dose escalation study to determine if axatilimab as monotherapy and axatilimab in combination with a fixed dose of durvalumab will be sufficiently safe and well-tolerated at biologically active doses to warrant further investigation in patients with solid tumors.

This is an open label, multi-center Phase 1 study consisting of Phase 1a and Phase 1b. The study will evaluate axatilimab monotherapy (in Phase 1a) and axatilimab combined with durvalumab (in Phase 1b) in patients with advanced solid tumors which must have progressed following prior treatment and have no standard therapy alternatives left (i.e., patients must not be candidates for regimens known to provide clinical benefit). The primary objective will be to determine the MTD and/or RP2D of axatilimab as monotherapy (Phase 1a) and in combination with durvalumab (Phase 1b) as evaluated by the incidence of AEs that are defined as DLTs. In both study phases, a standard "3+3" dose escalation schema will be used to determine an MTD with 3-6 evaluable patients enrolled per dose level. The RP2D will be determined based on data from the dose escalation patients as reviewed by the Safety Review Committee (SRC; comprised of investigators and the Sponsor).

Initially in both phases, 3 patients will receive axatilimab at 1 mg/kg IV on C1D1 and again on C1D15 of a 28-day cycle. Phase 1b only will also receive a fixed dose of 1500mg durvalumab IV on C1D1. If no DLTs are noted, 3 more patients will be treated at the next higher dose level (3 mg/kg). If 1 DLT is observed in 1 of 3 patients, 3 more patients will be treated at that starting dose level (1 mg/kg). If 2 or more DLTs are observed in 3-6 patients at the starting dose, the study will be terminated, or a lower dose will be considered. If the safety profile is acceptable, escalation to axatilimab doses of 3, 6 and 10mg/kg are planned for the 1a and for the 1b, doses of 3 and 6 mg/kg of axatilimab in combination with a fixed dose of 1500mg of durvalumab are planned. The MTD will be considered to have been exceeded if 2 or more patients in a dose group experience a DLT; in this case, the next lower dose group which has been evaluated will be considered as the MTD.

A Phase 1 Study to Investigate Axatilimab Alone or in Combination With Durvalumab in Patients With Solid Tumors

A Phase 1, Open-Label, Dose Escalation Trial to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Activity of SNDX-6352 Monotherapy and SNDX-6352 in Combination With Durvalumab in Patients With Unresectable, Recurrent, Locally-Advanced, or Metastatic Solid Tumors

To evaluate the change from Baseline in CSF-1 receptor occupancy (RO)

To investigate the relationship between candidate biomarkers (e.g., CSF-1, IL-34) and anti-tumor activity of axatilimab

To investigate the relationship between other biomarkers (e.g., tumor infiltrating lymphocytes, PD-L1, PD-1, PD-L2, circulating classical and non-classical CD-16 monocytes in blood) and anti-tumor activity of axatilimab

To characterize the relationship in change from baseline in plasma colony stimulating factor-1 \[CSF-1\] interleukin-34 \[IL-34\]), and IFN-gamma, IL-1beta, IL-2, IL-4, IL-5, IL-6, CXCL8/IL-8, IL-10, IL-12 (p70), IL-13, TNF-alpha, CD204/206 and sCD163 with systemic PK of axatilimab administered intravenously.

To characterize the pharmacodynamic (PD) profile of axatilimab and durvalumab when given in combination in patients with advanced solid tumors.

To evaluate the change from Baseline in CSF-1 receptor occupancy (RO).

To investigate the relationship between candidate biomarkers (e.g., CSF-1, IL-34) and anti-tumor activity of axatilimab when given in combination with a fixed dose of durvalumab.

To investigate the relationship between other biomarkers (e.g., tumor infiltrating lymphocytes, PD-L1, PD-1, PD-L2, circulating classical and non-classical CD-16 monocytes in blood) and anti-tumor activity of axatilimab when given in combination with a fixed dose of durvalumab.

To characterize the relationship in change from baseline in plasma colony stimulating factor-1 \[CSF-1\] interleukin-34 \[IL-34\]), and IFN-gamma, IL-1beta, IL-2, IL-4, IL-5, IL-6, CXCL8/IL-8, IL-10, IL-12 (p70), IL-13, TNF-alpha, CD204/206 and sCD163 with systemic PK of axatilimab administered intravenously when given in combination with a fixed dose of durvalumab.

All patients treated with axatilimab across all treatment arms (dosing levels) will have safety assessed in order to determine any dose-limiting toxicities (DLT)s.

All patients treated with axatilimab across all treatment arms (dosing levels) will have safety assessed in order to determine the MTD.

All patients treated with axatilimab across all treatment arms (dosing levels) will have safety assessed in order to determine the RP2D.

All patients treated with axatilimab in combination with a fixed dose of durvalumab across all treatment arms (dosing levels) will have safety assessed in order to determine any dose-limiting toxicities (DLT)s.

All patients treated with axatilimab in combination with a fixed dose of durvalumab across all treatment arms (dosing levels) will have safety assessed in order to determine the MTD.

All patients treated with axatilimab in combination with a fixed dose of durvalumab across all treatment arms (dosing levels) will have safety assessed in order to determine the RP2D.

Cmax for SDNX-6352 for axatilimab will be computed.

AUC for SDNX-6352 for axatilimab will be computed.

Tmax for SDNX-6352 for axatilimab will be computed.

T1/2 for SDNX-6352 for axatilimab will be computed.

To determine if the size and number of target lesions changes in response to treatment with axatilimab by analyzing CT-Scans/MRIs per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) and irRECIST.

To assess change from Baseline in plasma CSF-1 and IL-34 following IV administration

To assess the immunogenicity of axatilimab as measured by presence of anti-drug antibodies (ADA)

To assess the immunogenicity of durvalumab as measured by presence of anti-drug antibodies (ADA)

Syndax Pharmaceuticals

Skin and Connective Tissue Diseases

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Pembrolizumab

Immunomodulating Agents

Immune Checkpoint Inhibitors

Pembrolizumab 200 mg is administered intravenously at Week 1, then every 3 weeks during the treatment period (6 weeks). Therapy will continue for until initiation of SOC curative-intent treatment (neoadjuvant chemo therapy or surgery) at Week 7.

Radiation therapy (RT) consists of 8 Gy for 3 fractions over 3 consecutive days at Week 2.

Radiation Therapy

Axatilimab 1 mg/kg is administered intravenously weekly starting 1 week post- RT (Week 3). Therapy will continue until initiation of SOC curative-intent treatment (neoadjuvant chemo therapy or surgery) at Week 7.

Clinical Trial Recruitment Navigator

Stephen L Shiao, MD, PhD

This is an open-label prospective, single institution, Phase II study of pembrolizumab in combination with radiation therapy and CSF-1R inhibition in patients with high-risk TNBC. The primary objective is to assess the pathologic complete response (pCR) rate where pCR is defined as the absence of invasive disease in the breast and lymph nodes at the time of standard of care (SOC) treatment. Secondary objectives include evaluating the change in tumor infiltrating lymphocytes (TILs), safety and tolerability of the combination, progression-free survival, event-free survival, overall survival, and node clearance.

Reinvigorating TNBC Response to Immunotherapy With Combination Myeloid Inhibition and Radiation

IIT2021-01-Shiao-CSF1Ri: Reinvigorating TNBC Response to Immunotherapy With Combination Myeloid Inhibition and Radiation

The proportion of patients with absence of invasive disease in the breast and lymph nodes at the time of SOC curative-intent treatment.

An increase in the tumor-infiltrating lymphocyte score as measured by Salgado criteria, is an indicator of immune system engagement.

Adverse events are graded per NCI CTCAE v.5

The length of time from the start of study treatment to the first occurrence of recurrent disease, or death due to breast cancer.

Assessed from the start of study treatment until death due to any cause.

Assessed by the proportion of node-positive patients who become node-negative post study treatment (by EOT).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Axatilimab in Combination With Retifanlimab and Paclitaxel for the Treatment of Patients With Advanced or Metastatic Solid Tumors	NCT06320405	Advanced Malign... Metastatic Mali... Recurrent Malig... Refractory Mali...	Axatilimab Biopsy Biospecimen Col... Computed Tomogr... Magnetic Resona... Paclitaxel Positron Emissi... Retifanlimab	18 Years -	OHSU Knight Cancer Institute
A Phase 1 Study to Investigate Axatilimab Alone or in Combination With Durvalumab in Patients With Solid Tumors	NCT03238027	Solid Tumor Metastatic Tumo... Locally Advance... Unresectable Ma...	Axatilimab Durvalumab	18 Years -	Syndax Pharmaceuticals
Reinvigorating TNBC Response to Immunotherapy With Combination Myeloid Inhibition and Radiation	NCT05491226	TNBC - Triple-N... Breast Cancer	Pembrolizumab Radiation Thera... Axatilimab	18 Years -	Cedars-Sinai Medical Center
Reinvigorating TNBC Response to Immunotherapy With Combination Myeloid Inhibition and Radiation	NCT05491226	TNBC - Triple-N... Breast Cancer	Pembrolizumab Radiation Thera... Axatilimab	18 Years -	Cedars-Sinai Medical Center

Spots Global Cancer Trial Database for axatilimab

Every month we try and update this database with for axatilimab cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for axatilimab

Every month we try and update this database with for axatilimab cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for axatilimab cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.