Overview
T Cell Receptor-engineered T-cell therapy (TCR T-cell therapy) offers a potentially transformative approach to treating cancer, but is currently limited by the lack of known targets (Maus and June, 2016; Ping et al., 2018). Arguably the most clinically meaningful way to discover new targets and TCRs for TCR T-cell therapy is to study the tumor-infiltrating lymphocytes of patients that are actively responding to immune checkpoint inhibitor (ICI) therapy. These T cells are clonally expanded as a result of checkpoint inhibition and are responsible for the patient's clinical response. The goal of this study is to acquire tumor and blood samples from up to 200 patients with solid tumor malignancies who respond to ICI therapy. T cells will be isolated from these samples and the targets of their TCRs determined using TScan's genome-wide, high-throughput target ID technology. The expected outcome of this study is the discovery of a collection of new targets for TCR T-cell therapy, along with associated TCRs that will then be developed as novel therapies for patients with similar malignancies.
Eligibility
Inclusion Criteria:
Cohort Legend: Cohort 1: On-Treatment Responder (Biopsy), Cohort 2: Pre and On-Treatment
(Biopsy), Cohort 3: On-Treatment Responder (Surgery), Cohort 4: Post-Treatment Vitiligo,
Cohort 5: Post-Treatment Responder (Frozen)
1. Study Cohorts 1,2,3 and 5: Known or suspected diagnosis of non-hematological
malignancy.
2. Age 18 years at time of diagnosis.
3. Research Biopsy Study Cohorts 1 and 2: ECOG performance status 0-2.
4. Ability to understand and willingness to sign an informed consent document.
5. Research Biopsy Study Cohorts 1,2,3 and 5: Patients must be eligible for or currently
receiving treatment with immune checkpoint inhibitor (ICI) therapy as determined by
the patient's treating oncologist. The treatment regimen may comprise more than one
agent but must include at least one ICI drug. Examples of FDA-approved ICI drugs
include pembrolizumab (Keytruda), nivolumab (Opdivo), atezolizumab (Tecentriq),
avelumab (Bavencio), durvalumab (Imfinzi), cemiplimab (Libtayo), and ipilimumab
(Yervoy). Immune-checkpoint inhibitors not on this list may also be used, provided
they are FDA-approved.
6. Research Biopsy Study Cohorts 1,2,3 and 5: Patients undergoing an on-treatment biopsy
must show radiographic regression of one or more lesion, as assessed by the
investigator.
7. Research Biopsy Study Cohorts 1 and 2: Patients undergoing an on-treatment biopsy must
have a cancer lesion that is amenable for biopsy under local anesthesia or moderate
sedation per standard procedures. The tumor biopsy must have an acceptable clinical
risk, as judged by the investigator.
8. Research Biopsy Study Cohorts 1,2,4: Platelet count >50,000 prior to biopsy or per the
service performing the biopsy.
9. Research Biopsy Study Cohorts 1,2,4: Absolute neutrophil count >1500.
10. Research Biopsy Study Cohorts 1,2,4: Must be able to safely hold anticoagulants for 5
days prior to biopsy.
11. Research Biopsy Study Cohorts 1,2,4: Not receiving therapeutic anticoagulation at the
time of the biopsy. Patients on therapeutic anticoagulation must be able to safely
hold anticoagulation for the procedure with an acceptable risk, as judged by the
investigator. Patients who are on anticoagulation for clinical reasons and deemed
appropriate for biopsy must be OFF anticoagulation prior to biopsy as follows:
i. No warfarin (Coumadin) for 5 days. No low-molecular weight heparin (LMWH; e.g.
dalteparin/ Fragmin, enoxaparin/ Lovenox) for 24 hours.
ii. No fondaparinux/ Arixtra for 48 hours. iii. Patients receiving alternative forms of
anticoagulation not listed above (e.g., dabigatran, rivaroxaban, apixaban, edoxaban) should
consult with the prescribing physician and the service performing the biopsy regarding
safety and administration guidelines prior to biopsy. Bleeding risks with these agents
should be considered when deciding on whether to perform the biopsy if for research
purposes only.
Exclusion Criteria:
Cohort Legend: Cohort 1: On-Treatment Responder (Biopsy), Cohort 2: Pre and On-Treatment
(Biopsy), Cohort 3: On-Treatment Responder (Surgery), Cohort 4: Post-Treatment Vitiligo,
Cohort 5: Post-Treatment Responder (Frozen)
1. Concurrent disease or condition that would make the patient inappropriate for study
participation, or any serious medical or psychiatric disorder that would interfere
with safety.
2. Dementia, altered mental status, or any psychiatric condition that would prohibit the
understanding or rendering of informed consent.
3. Research Biopsy Study Cohorts 1,2,4: History of serious or life-threatening allergic
reaction to local anesthetics (i.e., lidocaine, xylocaine).
4. Pregnant women are excluded because there may be an increased risk to both mother and
fetus in the setting of moderate sedation, which is required for biopsies of certain
anatomic sites (e.g., liver, lung, bone). Also, ionizing radiation from CT-guided
biopsies may pose a risk to the unborn fetus.
5. Research Biopsy Study Cohorts 1,2,4: Active cardiac disease, defined as:
i. Uncontrolled or symptomatic angina within the past 3 months. ii. History of clinically
significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation,
torsades de pointes). Atrial fibrillation with controlled ventricular response on treatment
is not an exclusion.
iii. Myocardial infarction < 6 months from study entry. iv. Uncontrolled or symptomatic
congestive heart failure. f. Any other condition, which in the opinion of the patient's
treating oncologist or the physician performing the biopsy procedure, would make
participation in this protocol unreasonably hazardous for the patient.