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

Official Summary

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.

Eligibility Requirements

• Minimum Age: 18 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 50 participants

Study Arms

• Treatment (low dose, reduced frequency nivolumab) (EXPERIMENTAL)
  INDUCTION PHASE: Patients receive nivolumab 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 CT/MRI and blood sample collection throughout the study.

Interventions

• PROCEDURE: Biospecimen Collection — Undergo collection of urine and/or blood samples
• PROCEDURE: Computed Tomography — Undergo CT
• PROCEDURE: Magnetic Resonance Imaging — Undergo MRI
• BIOLOGICAL: Nivolumab — Given IV

Primary Outcomes

• Objective response (Up to 4 years after completion of study treatment)

Secondary Outcomes

• Duration of response (DOR) (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 (Up to 4 years after completion of study treatment)
• Progression free survival (PFS) (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) (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 (From date of first dose of study treatment until the date of death, assessed up to 4 years after completion of study treatment)

Eligibility Criteria

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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, an

Trial Locations

• Uganda Cancer Institute, Kampala, Uganda

Contact Information

• Shailender Bhatia, MD — CONTACT
  Phone: 206-606-6765
  Email: sbhatia@uw.edu

Study Officials

• Shailender Bhatia, MD — PRINCIPAL_INVESTIGATOR
  Fred Hutch/University of Washington Cancer Consortium

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