Trial Title:
Axatilimab in Combination With Retifanlimab and Paclitaxel for the Treatment of Patients With Advanced or Metastatic Solid Tumors
NCT ID:
NCT06320405
Condition:
Advanced Malignant Solid Neoplasm
Metastatic Malignant Solid Neoplasm
Recurrent Malignant Solid Neoplasm
Refractory Malignant Solid Neoplasm
Conditions: Official terms:
Neoplasms
Paclitaxel
Albumin-Bound Paclitaxel
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Axatilimab
Description:
Given IV
Arm group label:
Treatment (axatilimab, retifanlimab, paclitaxel)
Other name:
Anti-M-CSFR Monoclonal Antibody SNDX-6352
Other name:
SNDX 6352
Other name:
SNDX-6352
Other name:
SNDX6352
Other name:
UCB6352
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo tumor biopsy
Arm group label:
Treatment (axatilimab, retifanlimab, paclitaxel)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (axatilimab, retifanlimab, paclitaxel)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT scan
Arm group label:
Treatment (axatilimab, retifanlimab, paclitaxel)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (axatilimab, retifanlimab, paclitaxel)
Other name:
Magnetic Resonance
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Drug
Intervention name:
Paclitaxel
Description:
Given IV
Arm group label:
Treatment (axatilimab, retifanlimab, paclitaxel)
Other name:
Anzatax
Other name:
Asotax
Other name:
Bristaxol
Other name:
Praxel
Other name:
Taxol
Other name:
Taxol Konzentrat
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET scan
Arm group label:
Treatment (axatilimab, retifanlimab, paclitaxel)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron emission tomography (procedure)
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
Intervention type:
Biological
Intervention name:
Retifanlimab
Description:
Given IV
Arm group label:
Treatment (axatilimab, retifanlimab, paclitaxel)
Other name:
INCMGA 0012
Other name:
INCMGA-0012
Other name:
INCMGA00012
Other name:
INCMGA0012
Other name:
MGA 012
Other name:
MGA-012
Other name:
MGA012
Other name:
Retifanlimab-dlwr
Other name:
Zynyz
Summary:
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.
Detailed description:
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Ability to comprehend the investigational nature of the study and provide informed
consent. Written informed consent must be obtained prior to any study specific
procedures or interventions
- Age ≥ 18 years at the time of consent. All participants, irrespective of their
gender, gender identity, race, and ethnicity, will be included
- Certified, documented diagnosis of a metastatic solid tumor based on pathology
review
- Presence of at least one lesion that is measurable per Response Evaluation Criteria
in Solid Tumors (RECIST) 1.1 and another lesion that is amenable to tumor biopsy
- Relapsed from, or refractory to, standard of care (SOC) systemic therapy known to
prolong survival or if, in the opinion of the primary treating oncologist, a
clinical trial is the best option for the next line of treatment based on response
and/or tolerability to available therapies
- Investigational therapy is permitted after a wash-out period of 5 half-lives (if
known), or 28 days, whichever is shorter, prior to study day -8. Prior use of an
investigational agent for imaging, such as T cell imaging, is permitted
- Prior treatment with taxanes. A wash-out of period of ≥ 3 months prior to day -8
must be met for enrollment. Prior anti PD-1/PD-L1 therapy is allowed, but not
required
- Eastern Cooperative Oncology Group (ECOG) status (performance status [PS]) of 0-1
- Life expectancy of greater than 12 weeks according to certified physician review
- Hemoglobin (Hb) ≥ 8.5 g/dL
- Leukocytes ≥ 3,000/mcL
- Absolute neutrophil count (ANC) ≥ 1,500/mcL
- Platelets ≥ 100K/cc mL
- Values must be obtained without transfusion within 2 weeks
- Serum creatinine (sCr) < 1.5 x upper limit of normal (ULN) or creatinine clearance
(CrCl) ≥ 50 mL/min (calculated with the Cockcroft-Gault formula) for participants
with creatinine (sCr) levels above institutional normal
- Total bilirubin < 1.5 x upper limit of normal (ULN)
- With the exception of documented Gilbert's syndrome or similar conditions, at
the discretion of the principal investigator (PI). Clinical chemistry testing
may be adjusted, as clinically indicated
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) or
alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 x
ULN
- Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association (NYHA) Functional Classification. To
be eligible for this trial, patients should be class 2B or better
- Corrected QT interval Fridericia's formula (QTcF) of < 480 ms on a 12 lead
electrocardiogram (EKG), except for participants with atrioventricular pacemakers or
other conditions (e.g., right bundle branch block) that render the QT measurement
invalid
- Willingness to modify concomitant drug regimens, at the recommendation and
discretion of pharmacy services, including the use of known substrates or inhibitors
of CYP2C8 and CYP3A4
- Physiologic maintenance doses of corticosteroids (≤ 10 mg/day of prednisone or
equivalent) are permitted. Examples include: Asthma treatment; topical ocular,
intra-articular, or intranasal steroids with minimal systemic absorption; and brief
courses of corticosteroids for prophylaxis
- Patients with CD4+ T-cell (CD4+) counts ≥ 350 cells/uL are eligible regardless of
HIV serology
- HIV-infected patients on effective anti-retroviral therapy with undetectable
viral load within 6 months of enrollment are eligible
- In the case of ongoing treatment with antiretroviral therapy (ART), medication
adjustment may be necessary for the duration of treatment. A wash-out period
may be necessary, at the recommendation of the institutional research pharmacy
service (RPS)
- Evidence of chronic hepatitis B virus (HBV) infection (i.e., hepatitis B surface
antigen [HBsAg]-positive, undetectable or low HBV deoxyribonucleic acid [DNA], and
normal ALT) in the absence of HBV therapy, or serologic evidence of a resolved prior
HBV infection (i.e., HBsAg-negative and hepatitis B virus core antibody
[anti-HBc]-positive) is permitted
- History of hepatitis C virus (HCV) infection is permitted given prior curative
treatment or undetectable HCV viral load by serology or polymerase chain reaction
(PCR) testing
- Patient who are HCV antibody (Ab) seropositive but HCV ribonucleic acid (RNA)
negative due to prior treatment or natural resolution are eligible
Exclusion Criteria:
- Secondary malignancy with documented diagnosis by a treating physician < 3 years
prior to study day -8. The following criteria also apply:
- New or progressive brain metastases. Patients with brain metastases not
requiring immediate central nervous system (CNS) specific treatment or stable
for at least 4 weeks prior to study day -8 are eligible at the discretion of
the investigator given that neurologic symptoms are resolved.
- Patients with active leptomeningeal disease are not eligible
- Palliative radiation therapy administered within 1 week prior to study day -8, Note:
Participants must have recovered from all radiation-related toxicities (to grade < 1
or baseline), must not require corticosteroids for this purpose, and must not have
had radiation pneumonitis
- Immunization with a live vaccine within 28 days prior to study day -8
- History of organ transplantation, including hematopoietic stem cell transplantation
(HSCT)
- Clinical evidence of interstitial lung disease or active non-infectious pneumonia
- Active autoimmune disease requiring systemic immunosuppression in excess of
physiologic maintenance doses of corticosteroids (≤ 10 mg/day of prednisone or
equivalent is permitted)
- Prior National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events
(CTCAE) grade ≥ 3 immune-related adverse event (irAE) that required systemic
immunosuppression (endocrinopathies managed by stable doses of supplements and/or
corticosteroids ≤ 10 mg/day are permitted)
- Unresolved toxicities (resolution required to grade 1 or baseline) from prior
anticancer therapies. The following exceptions apply:
- Alopecia, lymphopenia, grade 2 neuropathy (if not resulting in functional
deficit), and grade 1 (no supplementation required) or grade 2 endocrinopathies
(stable on supplements)
- Prior allergy or severe hypersensitivity reaction to axatilimab, retifanlimab,
paclitaxel, cremaphor-containing agents, and/or components of the drug formulations
- Active infection requiring systemic antibiotic therapy
- Persons of childbearing potential (PCBP) who are pregnant (i.e., positive pregnancy
test within 7 days prior to study day -8) or breastfeeding are not eligible.
- The effects of the investigational regimen on the developing human fetus are
unknown. For this reason, persons of reproductive potential must agree to use a
highly effective form of contraception, starting with the time of consent to 4
months after the last dose of retifanlimab or 90 days after the last dose of
axatilimab, whichever is longer
- Sperm-producing participants must not donate sperm throughout the study period
and for 90 days post completion of study treatment
- Uncontrolled, intercurrent illness and psychiatric illness/social situations that
would limit compliance with study requirements, at the discretion of the
investigator
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
OHSU Knight Cancer Institute
Address:
City:
Portland
Zip:
97239
Country:
United States
Status:
Recruiting
Contact:
Last name:
Shivaani Kummar
Phone:
503-494-6594
Email:
kummar@ohsu.edu
Investigator:
Last name:
Shivaani Kummar
Email:
Principal Investigator
Start date:
May 31, 2024
Completion date:
April 1, 2029
Lead sponsor:
Agency:
OHSU Knight Cancer Institute
Agency class:
Other
Collaborator:
Agency:
Oregon Health and Science University
Agency class:
Other
Collaborator:
Agency:
Incyte Corporation
Agency class:
Industry
Source:
OHSU Knight Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06320405