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)

Overview

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.

Interventions

• Other Observation
  No intervention

Primary outcome measures

• Real-World Disease Free Survival (rwDFS) [Time frame: 5 years]
• Real-World Overall Survival (rwOS) [Time frame: 3 years]

Secondary outcome measures (10)

• Sensitivity, Specificity, PPV and NPV of MRD assay to predict recurrence at benchmark vs physician assessment of recurrence via conventional imaging every 6 months [Time frame: 5 years]
• 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 [Time frame: 5 years]
• Real-World Disease Free Survival (rwDFS) stratified by ctDNA status at benchmark [Time frame: 5 years]
• pCR rate stratified by ctDNA status [Time frame: 5 years]
• Real-World Overall Survival (rwOS) stratified by ctDNA status at benchmark [Time frame: 5 years]
• Positive percent agreement and negative percent agreement between plasma ctDNA vs tumor tissue at benchmark & longitudinal time points [Time frame: 5 years]
• Real-World Overall Survival [Time frame: 18 months]
• Real-World Progression-Free [Time frame: 18 months]
• Treatment patterns [Time frame: 18 months]
• Positive percent agreement and negative percent agreement between plasma ctDNA vs. tumor tissue at benchmark & longitudinal time points [Time frame: 18 months]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United States · 58 centers

• Alabama Oncology — Birmingham
• Mercy Clinic Oncology - Fort Smith — Fort Smith
• MemorialCare — Fountain Valley
• Cancer and Blood Specialty Clinic — Los Alamitos
• UCLA — Los Angeles
• Eastern CT and Hematology and Oncology Associates — Norwich
• Clermont Oncology Center — Clermont
• Woodlands Medical Specialists — Pensacola
• … and 50 more centers

Publications

• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020 Jan;70(1):7-30. doi: 10.3322/caac.21590. Epub 2020 Jan 8. PMID 31912902
• Duma N, Santana-Davila R, Molina JR. Non-Small Cell Lung Cancer: Epidemiology, Screening, Diagnosis, and Treatment. Mayo Clin Proc. 2019 Aug;94(8):1623-1640. doi: 10.1016/j.mayocp.2019.01.013. PMID 31378236
• Chansky K, Sculier JP, Crowley JJ, Giroux D, Van Meerbeeck J, Goldstraw P; International Staging Committee and Participating Institutions. The International Association for the Study of Lung Cancer Staging Project: prognostic factors and pathologic TNM stage in surgically managed non-small cell lung cancer. J Thorac Oncol. 2009 Jul;4(7):792-801. doi: 10.1097/JTO.0b013e3181a7716e. PMID 19458556
• Pignon JP, Tribodet H, Scagliotti GV, Douillard JY, Shepherd FA, Stephens RJ, Dunant A, Torri V, Rosell R, Seymour L, Spiro SG, Rolland E, Fossati R, Aubert D, Ding K, Waller D, Le Chevalier T; LACE Collaborative Group. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol. 2008 Jul 20;26(21):3552-9. doi: 10.1200/JCO.2007.13.9030. Epub 2008 May 27. PMID 18506026
• Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. doi: 10.1093/jnci/djr325. Epub 2011 Sep 8. PMID 21903745
• Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Kurata T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeno J, Faivre-Finn C, Reck M, Vansteenkiste J, Spigel DR, Wadsworth C, Melillo G, Taboada M, Dennis PA, Ozguroglu M; PACIFIC Investigators. Ove PMID 30280658
• Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. doi: 10.1056/NEJMoa011954. PMID 11784875
• Jordan EJ, Kim HR, Arcila ME, Barron D, Chakravarty D, Gao J, Chang MT, Ni A, Kundra R, Jonsson P, Jayakumaran G, Gao SP, Johnsen HC, Hanrahan AJ, Zehir A, Rekhtman N, Ginsberg MS, Li BT, Yu HA, Paik PK, Drilon A, Hellmann MD, Reales DN, Benayed R, Rusch VW, Kris MG, Chaft JE, Baselga J, Taylor BS, Schultz N, Rudin CM, Hyman DM, Berger MF, Solit DB, Ladanyi M, Riely GJ. Prospective Comprehensive M PMID 28336552

Identifiers

NCT: NCT05236114 · TP-CA-002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗