Early Clinical Evaluation of 18F-LY3546117 in Tumor Imaging

Study Overview
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Brief Summary
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Immuno-Oncology (IO) therapies have revolutionized cancer therapy and are becoming the standard of care for many cancers. Monitoring how well IO therapies work against cancer is difficult due to the complexity of the immune system and the fact that an immune response may initially increase, rather than decrease, the size of a tumor. An early response marker would be beneficial to determine which patients should remain on a given treatment or combination of treatments, and which patients should seek other treatment options. 18F-LY3546117 is a radiolabeled tracer that binds to a specific protein (Granzyme B) that is found in the human immune system and is thought to trigger programmed cell death. It is thought that imaging Granzyme B activity in tumors and elsewhere in the body using a Positron Emission Tomography (PET) scan will allow doctors to monitor the progress of IO therapy.

Official Title
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A Phase I Study Evaluating the Safety and Imaging Characteristics of 18F-LY3546117 Injection in Subjects Who Are Undergoing Treatment With Immune Checkpoint Inhibitors

Conditions
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Neoplasms, Neoplasms Malignant

Intervention / Treatment
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* Drug: 18F-LY3546117 Injection
* Procedure: PET Scan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Cohort 1): At least one imageable tumor greater than or equal to 15 mm in the longest diameter Confirmed diagnosis of cancer with a high likelihood of response to immuno-oncology therapy (melanoma or non-small cell lung cancer, or other malignancies with sponsor approval) and planned mono- or combination therapy with immuno-oncology therapy Life expectancy of greater than 6 months Inclusion Criteria (Cohort 2): At least one imageable tumor greater than or equal to 15 mm in the longest diameter or a tumor assessable by PET in the opinion of the radiologist Received treatment with an immune checkpoint inhibitor with evidence of response Life expectancy of greater than 6 months Exclusion Criteria: Subjects who plan to receive chemotherapy or radiation therapy during study participation Prior history of failed immune checkpoint inhibitor therapy Subjects who require steroid or other immunosuppressive medications within 2 weeks of the PET scan. Females of childbearing potential who are not surgically sterile, not refraining from sexual activity, or not using effective methods of contraception. Females of childbearing potential must not be pregnant or breastfeeding at screening and agree to avoid becoming pregnant for 24 hours following study drug administration. Females and males must agree to refrain from sexual activity or to use effective contraceptive methods for 24 hours following study drug administration and during study participation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 18F-LY3546117 Scan Cohort 1<br>18F-LY3546117 PET scan at baseline and between 14-42 days after initiation of immune checkpoint therapy | Drug: 18F-LY3546117 Injection<br>* 370 megabecquerel (MBq) intravenous injection<br>Procedure: PET Scan<br>* positron emission tomography (PET) scan<br>|
| Experimental: 18F-LY3546117 Scan Cohort 2<br>18F-LY3546117 PET scan at time of immune checkpoint therapy response | Drug: 18F-LY3546117 Injection<br>* 370 megabecquerel (MBq) intravenous injection<br>Procedure: PET Scan<br>* positron emission tomography (PET) scan<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 1: Uptake of 18F-LY3546117 in tumor foci and other organs of the body | Visual uptake in the tumor as assessed by sponsor expert reader (Yes/No) | Day 14 up to Day 42 of immune checkpoint inhibitor therapy | 
| Cohort 2: Uptake of 18F-LY3546117 in tumor foci and other organs of the body | Visual uptake in the tumor as assessed by sponsor expert reader (Yes/No) | At immune checkpoint inhibitor treatment response (Day 42 up to 6 months post-treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer Imaging