Low Dose, Reduced Frequency Nivolumab for the Treatment of Unresectable or Metastatic Cancer, AFFORD IO Trial

Официальное название

AFFORD IO: A Phase 2 Trial of Low Dose, Reduced Frequency Nivolumab (Anti-PD-1 Antibody) in Patients With Unresectable or Metastatic Cancer

Обзор

This phase II trial studies how well low dose, reduced frequency nivolumab works in treating patients with cancer that cannot be removed by surgery (unresectable) or that has spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Nivolumab is a type of immune checkpoint inhibitor (ICI). ICIs have revolutionized the treatment of numerous cancers with remarkable improvement in participant outcomes. However, accessibility of ICIs is extremely poor on a global scale, mainly due to high costs. Previous research has suggested that these drugs can be given at lower doses and reduced frequency than their approved dosing regimens, with similar results. Giving nivolumab at a lower dose and less often may help reduce the cost of therapy, improve immunotherapy accessibility, and therefore improve survival outcomes globally.

Подробное описание

OUTLINE:

INDUCTION PHASE: Patients receive nivolumab intravenously (IV) over approximately 30 minutes on days 1 and 45 in the absence of disease progression or unacceptable toxicity. Patients who are benefitting after 45 days proceed to Maintenance Phase.

MAINTENANCE PHASE: Patients receive nivolumab IV over approximately 30 minutes every 90 days (days 90, 180, 270 and 360) in the absence of disease progression or unacceptable toxicity.

All patients also undergo computed tomography (CT)/magnetic resonance imaging (MRI) and blood sample collection throughout the study. Patients may also undergo urine sample collection throughout the study.

After completion of study treatment, patients are followed up at 90 days and then every 12 months for up to 4 years.

Вмешательства

• Процедура Biospecimen Collection
  Undergo collection of urine and/or blood samples
• Процедура Computed Tomography
  Undergo CT
• Процедура Magnetic Resonance Imaging
  Undergo MRI
• Биопрепарат Nivolumab
  Given IV

Первичные конечные точки

• Objective response [Срок оценки: Up to 4 years after completion of study treatment]

Вторичные конечные точки (7)

• Duration of response (DOR) [Срок оценки: From the earliest date of disease response (CR or PR) until the earliest date of disease progression, or the date of death from any cause, assessed up to 4 years after completion of study treatment]
• Disease control [Срок оценки: Up to 4 years after completion of study treatment]
• Progression free survival (PFS) [Срок оценки: From date of first dose of study treatment until the earliest date of disease progression, or the date of death from any cause, assessed up to 4 years after completion of study treatment]
• Overall survival (OS) [Срок оценки: From date of first dose of study treatment until the date of death from any cause, assessed up to 4 years after completion of study treatment]
• Disease specific survival [Срок оценки: From date of first dose of study treatment until the date of death, assessed up to 4 years after completion of study treatment]
• Incidence of adverse events [Срок оценки: Up to 90 days years after completion of study treatment]
• Accrual and by compliance with treatment timepoints [Срок оценки: Up to 4 years after completion of study treatment]

Критерии участия

Критерии включения

• Participants are eligible if they have one of these histologically confirmed, unresectable or metastatic cancer types listed below, based upon historical responsiveness to anti-PD-(L)1 agents

• Non-small cell lung cancer (NSCLC) with documented PD-L1 expression (combined positive score \[CPS\] ≥ 1) (NOTE: Participants with known driver oncogenic mutations/rearrangements, including EGFR, ALK and ROS-1, will be excluded.)
• Head and neck squamous cell carcinoma (HNSCC) with documented PD-L1 expression (CPS ≥ 1)
• Clear cell renal cell carcinoma (ccRCC) (NOTE: Other subtypes may be permitted after approval by the Medical Monitor)
• Melanoma (cutaneous, acral-lentiginous and mucosal subtypes), and non-melanoma skin cancers, (cutaneous squamous cell carcinoma \[CSCC\], basal cell carcinoma \[BCC\] and Merkel cell carcinoma \[MCC\])
• Hodgkin's lymphoma
• Urothelial carcinoma
• Cervical cancer with documented PD-L1 expression (CPS ≥ 1)
• Colorectal cancer with high microsatellite instability (MSI) or mismatch repair deficiency
• Kaposi sarcoma (KS) without clinical concern for multicentric Castleman's disease (MCD)
• Any cancer type with historical data suggesting an ORR > 20% with anti-PD(L)-1 agents (NOTE: All participants in this category must be approved by the Medical Monitor prior to enrollment.)
• Must have experienced disease progression after or deemed not to be a good candidate for available curative systemic therapy options
• Presence of at least one measurable tumor, per RECIST v1.1
• Age 18 or older. (NOTE: Both men and women, and members of all races and ethnic groups are eligible for this trial.)
• Eastern Cooperative Oncology Group (ECOG) performance score of 0-2
• Absolute neutrophil count (ANC) ≥ 1.0 × 10\^9/L
• Platelet count ≥ 75 × 10\^9/L
• Hemoglobin ≥ 9 g/dL (NOTE: Participants may have been transfused)
• Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) (or total bilirubin ≤ 2.5 × upper limit of normal \[ULN\] in participants with Gilbert's syndrome)
• Estimated creatinine clearance ≥ 30mL/min according to the Cockcroft-Gault formula or according to local institutional standard
• Must consent to undergo serial research blood draws at study defined timepoints, unless deemed unsafe or not feasible by the treating investigator
• Must have an ability to understand and provide consent to the institutional review board (IRB)-approved informed consent form (ICF) document(s)
• Women of childbearing potential must have a negative serum or urine pregnancy test at screening
• Both male and female participants must be willing to use highly effective contraception, as stipulated in national or local guidelines, throughout the study and for at least 180 days after the last treatment administration, if the risk of conception exists

Критерии исключения

• Prior exposure to any immune-checkpoint inhibitor for any reason
• Residual adverse event(s) from prior therapy grade > 1 (National Cancer Institute \[NCI\]-Common Terminology Criteria for Adverse Events \[CTCAE\] v6.0) that could interfere with study endpoints or put participant safety at risk, as determined by the treating investigator
• Known active central nervous system (CNS) metastases and/or prior history of leptomeningeal cancer involvement
• Known history of another active malignancy (besides the eligible cancer diagnosis) within the last 3 years from day 1 of nivolumab that could interfere with study endpoints or put participant safety at risk. (NOTE: Exception will be made for adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ \[skin, bladder, cervical, colorectal, breast\] or low grade prostatic intraepithelial neoplasia or grade 1 prostate cancer. Any other neoplasm, which has been treated adequately and is adjudged by the treating investigator to have a low risk of progression during the study, could be enrolled only after approval from the medical monitor.)
• Known active hepatitis B virus (HBV) or hepatitis C virus (HCV), defined as follows:

• Active HBV is defined as a known positive hepatitis B virus surface antigen (HBsAg) result or positive total hepatitis B virus core antibody (anti-HBc) results in the absence of hepatitis B virus surface antibody (anti-HBsAb). (NOTE: When HBsAg is negative and HBcAb is positive, HBV-DNA should be measured. When HBV-deoxyribonucleic acid \[DNA\] is negative, this participant could be enrolled with close monitoring of HBV activities.)
• Active hepatitis C virus (HCV) is defined as a known positive HCV antibody result and quantitative HCV-ribonucleic acid (RNA) results greater than the lower limits of detection of the assay. (NOTE: Participants who have had definitive treatment for HCV are permitted if HCV-RNA is undetectable.)
• Known uncontrolled HIV infection. (NOTE: HIV-infected participants may be allowed if all the following criteria are met: CD4 count ≥ 100/μL, viral load less than 200 copies/mL, and clinically stable on antiretroviral therapy \[ART\] for at least 3 months.)

• These participants will be enrolled only after approval from the medical monitor
• Known active autoimmune disease or an allograft requiring systemic immunosuppression with corticosteroids (> 10 mg/day of prednisone or equivalent) or immunosuppressive drugs within the past 2 years before the first dose of nivolumab. (NOTE: Exceptions will be made for participants with autoimmune conditions such as diabetes type I, vitiligo, psoriasis, hypothyroid or hyperthyroid diseases not requiring immunosuppressive treatment; participants receiving physiologic corticosteroid replacement therapy at doses < 10 mg/day of prednisone or equivalent for adrenal or pituitary insufficiency; participants with a condition such as asthma or chronic obstructive pulmonary disease that requires intermittent use of steroids or those who require brief courses of corticosteroids for prophylaxis \[e.g., contrast dye allergy\], nivolumab-related standard premedication, and/or treatment of non-serious immune related adverse events. Any other situation must be discussed with the medical monitor for risk/benefit assessment.)
• Immunosuppressed status due to severe uncontrolled diabetes, concurrent uncontrolled hematological malignancy, or other comorbidities
• Known history of serious, active infections (aside from well-controlled HIV, as per exclusion criterion #6) requiring systemic antimicrobial agents within 14 days before the first dose of nivolumab. (NOTE: Chronic infections such as herpes simplex virus requiring suppressive therapy may be allowed after discussion with the medical monitor for risk/benefit assessment.)
• Known history of clinically significant interstitial lung disease, or active noninfectious pneumonitis
• Clinically significant (i.e., active) cardiovascular disease such as cerebral vascular accident or myocardial infarction within 6 months prior to first dose of nivolumab, ongoing unstable angina or congestive heart failure (New York Heart Association Classification class II-IV), or serious cardiac arrhythmia that could jeopardize participant safety on the study
• Receipt of live vaccine(s) within 30 days of planned start of nivolumab. (NOTE: Examples of live vaccines include but are not limited to measles, mumps, rubella, varicella-zoster \[chickenpox\], yellow fever, rabies, bacillus Calmette Guerin \[BCG\], and typhoid vaccines. Seasonal influenza vaccines for injection are generally killed-virus vaccines and are allowed; however, intranasal influenza vaccines are live, attenuated vaccines and are not allowed.)
• Known severe acute or chronic medical conditions such as uncontrolled seizure disorder, serious psychiatric illness, or laboratory abnormalities, that may increase the risk associated with study participation or may interfere with the interpretation of study endpoints and, in the judgment of the treating investigator, would make the participant inappropriate for entry into this study
• Known active tuberculosis (TB). (NOTE: Participants with latent TB will be allowed, provided they are receiving tuberculosis preventive therapy, after approval of the medical monitor.)
• Known allergy or hypersensitivity to any component of the study drug formulation (including excipients and additives) that could interfere with study endpoints or put participant safety at risk
• Pregnant or breast-feeding woman

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Uganda · 1 центр

• Uganda Cancer Institute — Kampala

Идентификаторы

NCT: NCT07576725 · RG1125119 · NCI-2026-01874

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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