Clinical trial NCT05236114: GEMINI-NSCLC: NSCLC Biomarker Study
Official title: TEMPUS GEMINI NSCLC STUDY: A Longitudinal Multi-Omic Biomarker Profiling Study of Patients With Non-Small Cell Lung Cancer (NSCLC)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Non-Small Cell Lung Cancer
Keywords: Cancer
Oncology
Observational
Genomic Profiling
Precision medicine
Non-Small Cell Lung Cancer
NSCLC
NGS
Biomarkers
Lead sponsor: Tempus AI
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
First posted: 2022-02-11
Enrollment: 1200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This protocol targets patients with Non-Small Cell Lung Cancer (NSCLC)

Brief summary: GEMINI NSCLC Study is a non-interventional study that will be collecting clinical and molecular health information from patients with NSCLC who will receive longitudinal blood collection in addition to their standard of care therapy and disease surveillance with the goals of identifying the molecular evolution of lung cancer with standard of care therapy, and determining the utility of ctDNA dynamics to predict risk of recurrence and therapeutic outcomes.


Eligibility criteria: For Cohort 1 Inclusion, the participant has/is:

* A known or suspected NSCLC treated with curative intent -(surgery with or without perioperative (neoadjuvant or adjuvant) therapy).

  * Suspected NSCLC - Patients with a high index of suspicion for the diagnosis of NSCLC that is resectable may sign informed consent prior to undergoing diagnostic procedure at the discretion of the physician. NCCN Guidelines allow for clinical stage IA cancers to proceed directly to definitive surgery. Per NCCN Guidelines, if a preoperative tissue diagnosis has not been obtained, then an intraoperative diagnosis will be obtained. If a diagnosis of NSCLC is not confirmed and/or the tumor is not resectable, then the patient will be a screen failure.
* Undergone or planning to undergo a surgical resection - (Patients with stages I-IIIB who are resectable - per NCCN guidelines of resectability)
* Both patients who lack molecular abnormalities and those with identified molecular abnormalities may enroll. Choice of perioperative therapy is to follow SOC therapeutic guidelines for the participant's molecular and PD-L1 profile.
* 18 years old or older
* Willing and able to provide informed consent
* Willing to have additional blood samples collected during routine surveillance visits
* Must submit tumor sample representative of current disease

For Cohort 1 Exclusion, the participant has/is:

* Patients with superior sulcus tumors who are candidates for preoperative concurrent chemoradiation.
* Stage III locally advanced and unresectable patients who are candidates for chemoradiation followed by immunotherapy.
* It is expected that all patients on the cohort will be treated with a definitive surgical resection. Thus, clinical stage IIIB and IIIC patients who subsequently demonstrate pathologically confirmed N3 nodal disease or T4 N2 or 3 per any confirmatory procedure listed in NCCN guidelines for which definitive chemoradiotherapy rather than surgery is recommended per NCCN Guidelines are not eligible.
* Patients who receive primary radiation (in lieu of surgery if they are not surgical candidates).

For Cohort 2 Inclusion, the participant has/is:

* Histologically documented Stage IV NSCLC (de novo metastatic or relapse setting) not amenable to curative surgery or radiation therapy. Palliative radiation (for instance for impending bony fracture or to control pain) is allowed at any time during the protocol at the physician's discretion.
* Intended to receive first line immunotherapy (as monotherapy or in combination with chemotherapy). Patients who have had previous exposure to immunotherapy in the neoadjuvant or adjuvant setting are allowed to enroll as long as 12 months have elapsed since the prior exposure.

  * Patients in surveillance on Cohort 1 are eligible to roll over to Cohort 2 at the time of recurrence as long as they have had histologic confirmation of recurrence and have been off immunotherapy for 12 months or greater and meet all other inclusion/exclusion criteria.
* Tumors that lack activating EGFR mutations (e.g., exon 19 deletion or exon 21 L858R, exon 21 L861Q, exon 18 G719X, or exon 20 S768I mutation) and ALK fusions. Also, per NCCN Guideline recommended testing, tumors must also lack ROS1, BRAF, NTRK 1/2/3, METex14 skipping mutations, and RET for which there is available front-line targeted therapy. Only those patients with KRAS G12C mutations and ERBB2 (HER2) mutations with no contraindications to immunotherapy (PD-L1 1) for which there are no approved front-line targeted therapies and for whom immunotherapy would be the preferred front-line therapy are eligible.
* Patients may be enrolled with local molecular testing and those results will be provided.

  * Patients may be enrolled with local molecular testing and those results will be provided.
* 18 years and older
* Willing and able to provide informed consent
* Willing to have additional blood samples collected during routine surveillance visits
* Must submit tumor sample representative of current disease

Exclusion Criteria (both Cohorts):

* Patients without a known or suspected NSCLC diagnosis, or other disease processes such as sarcoidosis, lymphoma, or metastatic cancer from other sites.
* Not willing to have additional blood samples collected
* Patients with a secondary malignancy must have been both diagnosed \> 2 years from the lung cancer of interest and have completed all therapy for that malignancy (including extended adjuvant therapy) \> 2 years prior to diagnosis of the lung cancer of interest with the exception of the following:
* Patients with superficial basal cell carcinoma of low-risk histology per NCCN Guidelines (Low-risk histologic subtypes include nodular, superficial, and other non-aggressive growth patterns such as keratotic, infundibulocystic, and fibroepithelioma of Pinkus) and low-risk for recurrence per NCCN Guidelines (location on trunk or extremities, size \< 2 cm, primary (not recurrent), with well-defined borders) can be included even if they are diagnosed \< 2 years from the lung cancer of interest.
* Patients with superficial squamous cell carcinoma of low-risk pathology per NCCN Guidelines (verrucous, keratoacanthomatous) and low-risk for recurrence per NCCN Guidelines (located on trunk or extremities; 2 cm in size; primary lesion (vs. recurrent); well to moderately differentiated; \< 2 mm thick and no invasion beyond subcutaneous fat; negative for perineural invasion; and negative for lymphatic or vascular involvement) can be included even if they are diagnosed \< 2 years from the lung cancer of interest.

Primary outcomes:
measure: Real-World Disease Free Survival (rwDFS)
timeFrame: 5 years
measure: Real-World Overall Survival (rwOS)
timeFrame: 3 years
Secondary outcomes:
measure: Sensitivity, Specificity, PPV and NPV of MRD assay to predict recurrence at benchmark vs physician assessment of recurrence via conventional imaging every 6 months
timeFrame: 5 years
measure: Sensitivity, Specificity, PPV and NPV of MRD assay to predict recurrence across longitudinal collections vs physician assessment of recurrence via conventional imaging every 6 months
timeFrame: 5 years
measure: Real-World Disease Free Survival (rwDFS) stratified by ctDNA status at benchmark
timeFrame: 5 years
measure: pCR rate stratified by ctDNA status
timeFrame: 5 years
measure: Real-World Overall Survival (rwOS) stratified by ctDNA status at benchmark
timeFrame: 5 years
measure: Positive percent agreement and negative percent agreement between plasma ctDNA vs tumor tissue at benchmark & longitudinal time points
timeFrame: 5 years
measure: Real-World Overall Survival
timeFrame: 18 months
measure: Real-World Progression-Free
timeFrame: 18 months
measure: Treatment patterns
timeFrame: 18 months
measure: Positive percent agreement and negative percent agreement between plasma ctDNA vs. tumor tissue at benchmark & longitudinal time points
timeFrame: 18 months
Other outcomes:
measure: Prevalence of genomic variants at landmark timepoints
timeFrame: 5 years
measure: Compare ctDNA levels detected before and after biopsy
timeFrame: 5 years
measure: Prevalence of genomic variants at landmark timepoints
timeFrame: 18 months
measure: Identification of the emergence of genomic variants and tumor biologic subclones over time with early-stage and advanced stage lung cancer
timeFrame: 5 years
measure: Identify genomic determinants of disease recurrence or progression.
timeFrame: 5 years
measure: Define ctDNA status at clinically-meaningful timeframes: at completion of neoadjuvant therapy, at the completion of surgery, at the completion of adjuvant therapy, and 30 days post completion of all therapy.
timeFrame: 5 years
measure: Correlate ctDNA clearance with the ability to obtain pCR
timeFrame: 5 years
measure: Correlate ctDNA detection rate with stage of disease (stages I - III)
timeFrame: 5 years
measure: Define ctDNA dynamics at specified surveillance timepoints and correlate with simultaneous imaging and clinical disease status
timeFrame: 5 years
measure: Define PPV of ctDNA to predict recurrence
timeFrame: 5 years
measure: Correlate ctDNA clearance (or lack of clearance) with rwPFS and rwOS.
timeFrame: 18 months
Locations:
city: Birmingham
country: United States
facility: Alabama Oncology
state: Alabama
city: Fort Smith
country: United States
facility: Mercy Clinic Oncology - Fort Smith
state: Arkansas
city: Fountain Valley
country: United States
facility: MemorialCare
state: California
city: Los Alamitos
country: United States
facility: Cancer and Blood Specialty Clinic
state: California
city: Norwich
country: United States
facility: Eastern CT and Hematology and Oncology Associates
state: Connecticut
city: Clermont
country: United States
facility: Clermont Oncology Center
state: Florida
city: Pensacola
country: United States
facility: Woodlands Medical Specialists
state: Florida
city: Atlanta
country: United States
facility: Morehouse School of Medicine (MSM)
state: Georgia
city: Atlanta
country: United States
facility: Piedmont Healthcare
state: Georgia
city: Honolulu
country: United States
facility: Hawaii Cancer Care
state: Hawaii
city: Carterville
country: United States
facility: Southern Illinois Hospital Services
state: Illinois
city: Decatur
country: United States
facility: Cancer Care Specialists of Illinois
state: Illinois
city: Evanston
country: United States
facility: Northwestern University
state: Illinois
city: Hinsdale
country: United States
facility: Hope and Healing Cancer Services
state: Illinois
city: Rockford
country: United States
facility: OSF Saint Anthony Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Community Health Network
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Bethesda
country: United States
facility: The Center for Cancer and Blood Disorder
state: Maryland
city: Frederick
country: United States
facility: Frederick Health Regional System
state: Maryland
city: Joplin
country: United States
facility: Mercy Clinic Oncology and Hematology - Joplin
state: Missouri
city: Osage Beach
country: United States
facility: Lake Regional Health System
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Clinic Oncology and Hematology - Sindelar Cancer Center
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Clinic Oncology and Hematology - David C. Pratt Cancer Center
state: Missouri
city: Springfield
country: United States
facility: Mercy Clinic Cancer and Hematology - Chub O'Reilly Cancer Center
state: Missouri
city: Springfield
country: United States
facility: Oncology Hematology Associates
state: Missouri
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Las Vegas
country: United States
facility: OptumCare Cancer Care
state: Nevada
city: Las Vegas
country: United States
facility: Hope Cancer Care of Nevada
state: Nevada
city: Reno
country: United States
facility: Cancer Care Specialists Reno
state: Nevada
city: Belleville
country: United States
facility: New Jersey Cancer Center
state: New Jersey
city: Albany
country: United States
facility: New York Oncology Hematology
state: New York
city: East Syracuse
country: United States
facility: Hematology Oncology Associates of Central New York
state: New York
city: Ithaca
country: United States
facility: Cayuga Medical Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: White Plains
country: United States
facility: White Plains Hospital
state: New York
city: Chapel Hill
country: United States
facility: UNC
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Goldsboro
country: United States
facility: Southeastern Medical Oncology Center (SMOC)
state: North Carolina
city: Canton
country: United States
facility: Aultman Hospital
state: Ohio
city: Cincinnati
country: United States
facility: TriHealth Cancer Institute
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Columbus
country: United States
facility: OhioHealth Reseach Institute
state: Ohio
city: Maumee
country: United States
facility: Taylor Cancer Research Center
state: Ohio
city: Oklahoma City
country: United States
facility: Hightower Clinical
state: Oklahoma
city: Oklahoma City
country: United States
facility: Mercy Clinic Oncology and Hematology - Coletta
state: Oklahoma
city: Tulsa
country: United States
facility: Oklahoma Cancer Specialists and Research Institute
state: Oklahoma
city: Salem
country: United States
facility: Oregon Oncology Specialists
state: Oregon
city: York
country: United States
facility: Cancer Care Associates of York
state: Pennsylvania
city: Charleston
country: United States
facility: The Medical University of South Carolina
state: South Carolina
city: Memphis
country: United States
facility: Baptist Cancer Center
state: Tennessee
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Bellingham
country: United States
facility: PeaceHealth St. Joseph Medical Center-Bellingham
state: Washington
city: Spokane Valley
country: United States
facility: Cancer Care Northwest
state: Washington
city: Appleton
country: United States
facility: ThedaCare Regional Cancer Center
state: Wisconsin
city: La Crosse
country: United States
facility: Gundersen Health System
state: Wisconsin
Study officials:
affiliation: Tempus AI, Inc.
name: Virginia Rhodes, MD
role: PRINCIPAL_INVESTIGATOR
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