RECRUITING

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

Conditions

Advanced Malignant Solid Neoplasm Metastatic Malignant Solid Neoplasm Recurrent Malignant Solid Neoplasm Refractory Malignant Solid Neoplasm

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2024-05-31

Study Completion:2029-04-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06320405

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	* 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

Inclusion Criteria

Exclusion 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

* 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

Contacts and Locations

Principal Investigator

Shivaani Kummar

PRINCIPAL_INVESTIGATOR

OHSU Knight Cancer Institute

Study Locations (Sites)

OHSU Knight Cancer Institute

Portland, Oregon, 97239

United States

Collaborators and Investigators

Sponsor: OHSU Knight Cancer Institute

Shivaani Kummar, PRINCIPAL_INVESTIGATOR, OHSU Knight Cancer Institute

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-05-31

Study Completion Date2029-04-01

Study Record Updates

Study Start Date2024-05-31

Study Completion Date2029-04-01

Terms related to this study

Additional Relevant MeSH Terms

Advanced Malignant Solid Neoplasm
Metastatic Malignant Solid Neoplasm
Recurrent Malignant Solid Neoplasm
Refractory Malignant Solid Neoplasm