Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study

Knight Cancer Institute Study of Histology-Agnostic Immunotherapy With Focus on Timing: - Knight SHIFT - A Prospective, Multi-Histology Pragmatic Study

This phase IV trial is evaluating whether morning versus afternoon administration of standard of care immunotherapy impacts its effectiveness in treating patients with solid tumors 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). Immunotherapy with monoclonal antibodies may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Circadian rhythm refers to the internal biological clock in which various processes in the body, including immune cell activity, are controlled by the time of day. Exactly how this works is not fully understood, and the researchers want to see if circadian rhythm control of the immune system can influence response to immunotherapy based on whether it is given in the morning (before 11:00 am) or afternoon (12:00pm). The time of day that immunotherapy is given (morning versus afternoon) may impact the effectiveness in treating patients with advanced or metastatic solid tumors.

PRIMARY OBJECTIVE:

I. To compare progression-free survival among participants receiving immunotherapy based on time of day (ToD) administration (early versus [vs.] late).

SECONDARY OBJECTIVES:

I. To compare overall survival among participants receiving immunotherapy based on ToD administration (am vs. pm).

II. To compare rates of significant immune-related adverse events (irAEs) based on ToD administration (am vs. pm).

EXPLORATORY OBJECTIVES:

I. To compare objective responses among participants receiving immunotherapy based on ToD administration (am vs. pm).

II. To compare disease control among participants receiving immunotherapy based on ToD administration (am vs. pm).

III. To compare the duration of response among participants receiving immunotherapy based on ToD administration (am vs. pm).

OUTLINE: Patients are randomized to 1 of 2 cohorts.

AM COHORT: Patients receive standard of care immunotherapy before 10:30 for 4 doses in the absence of disease progression or unacceptable toxicity. Subsequent doses may be given per standard of care timing. Patients also undergo blood sample collection throughout the study.

PM COHORT: Patients receive standard of care immunotherapy after 13:30 for 4 doses in the absence of disease progression or unacceptable toxicity. Subsequent doses may be given per standard of care timing. Patients also undergo blood sample collection throughout the study.

After completion of immunotherapy treatment, patients are followed up every 6 months for 2 years.

Inclusion Criteria:

• Must provide written informed consent before any study-specific procedures or interventions are performed

• Aged ≥ 18 years

• Histologically confirmed advanced/metastatic solid tumor as follows:

  • Non small cell lung cancer (NSCLC) (driver-negative, immune checkpoint inhibitor [ICI]-eligible)
  • Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) (platinum-eligible),
  • Renal cell carcinoma (RCC)
  • Biliary-tract cancer (BTC)
  • Hepatocellular carcinoma (HCC)
  • Melanoma

• Planned to receive a Food and Drug Administration (FDA)-approved immune check point inhibitor (e.g., anti-PD-1, anti-PD-L1, anti-CTLA4) regimen for the treatment of their malignancy

• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Exclusion Criteria:

• Prior ICI-based regimen for treatment of cancer
• Current or prior use of immunosuppressive medication within 28 days before planned standard-of-care immunotherapy infusion, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses not exceeding 10 mg/day of prednisone (or equivalent corticosteroid)
• Uncontrolled autoimmune disease requiring immunosuppression
• Active, uncontrolled central nervous system (CNS) metastases