Off-Label Treatment With Immune Checkpoint Inhibitor Blockade

This is a phase II therapeutic interventional clinical trial that will evaluate the efficacy, safety, and outcomes of off-label immune checkpoint blockade use across malignancies.

Study Overview

• Status: Not yet recruiting
• Conditions: Malignancy
• Intervention / Treatment: Drug: One or more off-label ICIs alone or with other on-label ICI(s); Drug: Off-label ICI(s) with targeted therapy; Drug: off-label ICI(s) with other agents that are not targeted (including, but not limited to, chemotherapy, hormonal therapy, immunotherapy other than ICIs) with or without targeted agents

Detailed Description

Subjects will be in one of the three following groups (n=69 for each group), depending on the therapy administered:

• Treatment Group A: One or more off-label immune checkpoint inhibitor (ICI) (s) alone or with other on-label ICI(s).
• Treatment Group B: Off-label ICI(s) with targeted therapy.
• Treatment Group C: Off-label ICI(s) with other agents that are not targeted (including, but not limited to, chemotherapy, hormonal therapy, and immunotherapy other than ICIs) with or without targeted agents.

At least one ICI agent must be off-label, and no agent can be investigational; agents other than ICI can be on-label or off-label, but all have to be FDA-approved.

• Study Type: Interventional
• Enrollment (Estimated): 231
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Medical College of Wisconsin Cancer Center Clinical Trials Office; Phone Number: 8900 866-680-0505; Email: cccto@mcw.edu

Study Locations

• United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert & the Medical College of Wisconsin
      • Contact: Razelle Kurzrock, MD; Phone Number: 414-955-2848; Email: rkurzrock@mcw.edu
      • Principal Investigator: Razelle Kurzrock, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years.
• Zubrod Performance Status 0-2.
• Patients must have a documented malignancy where an off-label ICI is being considered by a physician.

• Patients must have adequate organ function as specified below:

  • Absolute Neutrophil Count (ANC) ≥1,000/mcL
  • Platelets ≥75,000/mcL
  • Total Bilirubin ≤2.0 × upper limit of normal (ULN), unless the patient has changes consistent with Gilbert's Syndrome.
  • Alanine Aminotransferase (ALT) ≤3.0 × ULN
  • Serum Creatinine ≤2.0 × ULN or CrCl ≥50 mL/min as calculated by the Cockcroft-Gault equation.
• 5. Females of child-bearing potential must have a negative pregnancy test and must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from the time of informed consent, for the duration of study participation, and for 6 months following completion of therapy. Should a female patient become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception from the time of informed consent, for the duration of study participation, and 6 months after completion of administration.

NOTE: A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

• Has not undergone a hysterectomy or bilateral oophorectomy

• Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)

  • Ability to understand a written informed consent document and the willingness to sign it.
  • Physician has verified coverage of the cost of the drug(s) via insurance, specialty pharmacy, patient assistance programs, or other means, as documented by physician/mid-level or nursing notes, pharmacist notes, or MCW/FH insurance approval.

Exclusion Criteria:

• Uncontrolled illness, including symptomatic congestive heart failure (NYHA III/IV), unstable angina, or cardiac procedure within 2 weeks of start of ICI.
• Concurrent therapy: use of other investigational (no FDA approval for any indication) anti-cancer agents within 14 days of registration.
• Although other therapy is allowed together with the off-label ICI use as outlined in the protocol, before starting the study ICI off-label drug, the patient must be off other anti-cancer therapies for at least 2 weeks or 5 half-lives, whichever is shorter.
• Major surgery (as defined by the treating medical oncologist) within two weeks of the start date of immunotherapy.
• Other: pregnancy or lactation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: One or more off-label ICI(s) alone or with other on-label ICI(s).; Study drug(s) will be administered at the discretion of the treating medical oncologist in accordance with the FDA-approved prescribing information for each agent and applicable institutional standards of care.	Drug: One or more off-label ICIs alone or with other on-label ICI(s); Subjects will receive one of three ICI regimens, as prescribed by their treating medical oncologist.
Experimental: Off-label ICI(s) with targeted therapy; Study drug(s) will be administered at the discretion of the treating medical oncologist in accordance with the FDA-approved prescribing information for each agent and applicable institutional standards of care.	Drug: Off-label ICI(s) with targeted therapy; Subjects will receive one of three ICI regimens, as prescribed by their treating medical oncologist.
Experimental: Off-label ICI(s) with other agents that are not targeted with or without targeted agents.; Not targeted includes, but is not limited to chemotherapy, hormonal therapy, immunotherapy other than ICIs. Study drug(s) will be administered at the discretion of the treating medical oncologist in accordance with the FDA-approved prescribing information for each agent and applicable institutional standards of care.	Drug: off-label ICI(s) with other agents that are not targeted (including, but not limited to, chemotherapy, hormonal therapy, immunotherapy other than ICIs) with or without targeted agents; Subjects will receive one of three ICI regimens, as prescribed by their treating medical oncologist.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response.	The proportion of subjects who achieve complete response, partial response, or stable disease of at least 6 months, as evaluated by a physician investigator, who can use RECIST v1.1 and iRECIST. For non-solid malignancies, the standard evaluation criteria for that malignancy will be used.	at least 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious adverse events	The number of Grade ≥3 serious adverse events at least possibly related to ICIs during treatment, per NCI CTCAE v6.0.	Up to 5 Years
Progression-Free Survival	Time from the start of off-label ICI treatment to the earliest date of documented progression, symptomatic deterioration, start of new anti-cancer therapy, or death from any cause. Progression is assessed by the treating medical oncologist. Patients alive without reported progression (including no evaluation) are censored at last contact.	Up to 5 years
Overall Survival	Time from the start of off-label ICI treatment to the date of death from any cause. Patients last known to be alive are censored at the date of last contact.	Up to 5 years

Collaborators and Investigators

• Sponsor: Medical College of Wisconsin
• Investigators: Principal Investigator: Razelle Kurzrock, MD, Medical College of Wisconsin

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): November 1, 2032
• Study Completion (Estimated): November 1, 2036

Study Registration Dates

• First Submitted: August 4, 2026
• First Submitted That Met QC Criteria: August 4, 2026
• First Posted (Actual): August 10, 2026

Study Record Updates

• Last Update Posted (Actual): August 10, 2026
• Last Update Submitted That Met QC Criteria: August 4, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: immune checkpoint inhibitor
• Additional Relevant MeSH Terms: Neoplasms; Therapeutics; Drug Therapy
• Other Study ID Numbers: PRO00059781

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes