Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Durvalumab

Antineoplastic Agents, Immunological

Subjects with detectable ctDNA (MRD+) will receive up to 12 cycles of durvalumab (1500mg dose by intravenous (by vein) injection every 28 days). ctDNA will be re checked following 2 cycles (8 weeks) of durvalumab and compared to baseline levels. In the absence of progression or toxicity after 2 cycles, subject will continue with durvalumab to complete 1 year of treatment about 10 additional cycles).

Subjects will be monitored for secondary endpoints of progression free survival (PFS) and overall survival (OS).

Subjects with undetectable ctDNA (MRD) will receive Standard of care and no treatment

Roche Sequencing and Life Science kit to detect minimal residue disease (MRD)

AVENIO ctDNA Surveillance Kit

1500mg intravenous dose or 20mg/kg if weight is 30kg or less, manufactured by AstraZeneca

Laura Lundi, BS

Grace Hwang, BS

Grace Hwang

Joel W Neal, MD, PhD

Joel W Neal, MD,PhD

In this study circulating tumor DNA (ctDNA) blood testing is used to detect the residual blood cancer. If residual cancer using this blood test is detected there may be at higher risk of having the cancer return. The study is going to test whether or not the number of circulating cancer cells detected in the blood can be reduced by administration durvalumab after the standard treatment if you are tested positive for the residual cancer.

Primary Objective:

The primary objective of this study is to measure the change in ctDNA from trial enrollment to after 2 cycles of adjuvant durvalumab in subjects with stage I to III NSCLC who had positive ctDNA following definitive treatment with surgery or radiation and completion of adjuvant standard of care chemotherapy. Secondary Objectives

1. To compare disease free survival (DFS)
2. To compare overall survival (OS)
3. To evaluate the frequency and severity of toxicity
4. To evaluate the severity of toxicity

Adjuvant ctDNA-Adapted Personalized Treatment in Early Stage NSCLC (ADAPT-E)

Change in minimal residual disease (MRD) will be assessed on the basis of reduction of circulating tumor DNA (ctDNA) in the blood of participants in Cohort 1 MRD+ only. ctDNA is an indicator of MRD. The outcome will be reported as the number of participants who have a ≥ 3-fold drop in ctDNA levels after 2 cycles of durvalumab treatment, a number without dispersion.

Circulating tumor DNA (ctDNA) in the blood is an indicator of minimal residual disease (MRD), a risk factor for future relapse or progression. The outcome will be reported as the number of Cohort 1 MRD+ participants for whom, following 2 cycles of durvalumab, ctDNA was detected, not detected, or unable to be determined, each a number without dispersion. Available data for Cohort 2 MRD- participants will also be reported for the 8-week timepoint.

Overall survival (OS) defined as the duration from study registration until death due to any cause. The outcome will be reported as the number of participants in each cohort known to be alive at 12 months after study registration, a number without dispersion.

Disease-free survival (DFS) is defined as the number of participants remaining alive without disease progression (DP), symptomatic deterioration, or death due to any cause. DP is assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria, as follows.

* Complete Response (CR) = Disappearance of all target lesions
* Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions
* Progressive disease (PD) = 20% increase in the sum of the diameters of target lesions (must be \> 5 mm), unequivocal progression of non-target lesions, and/or the appearance of one or more new lesion(s)
* Stable disease (SD) = Small changes that do not meet any of the above criteria The outcome will be reported as the number of participants who meet the criteria for DFS, a number without dispersion.

Related adverse events (AEs) are deleterious events determined to be possibly, probably, or definitely-related to durvalumab treatment. The outcome will be reported as the number of related AEs experienced by the participants in Cohort 1 MRD+ only (ie, durvalumab treatment cohort), a number without dispersion.

AstraZeneca

Stanford University

Micronutrients

Hematinics

Amino Acids

Vitamins

Paclitaxel

Carboplatin

Pemetrexed

Albumin-Bound Paclitaxel

Cisplatin

Immunomodulating Agents

Tremelimumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Tubulin Modulators

Antimitotic Agents

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunologic Factors

Glutamic Acid

Folinic Acid

Folate

Vitamin B9

Subjects with detectable ctDNA will receive 4 cycles of platinum doublet chemotherapy \[carboplatin/pemetrexed\], tremelimumab (75 mg IV every 21 days) and durvalumab (1500 mg IV every 21 days), except subjects with squamous cell carcinoma histology will receive carboplatin/paclitaxel. Subjects will be evaluated with PET/CT and/or computed tomography (CT) thorax every 12 weeks. Following ctDNA evaluation, in the absence of progression or toxicity, subject will continue with durvalumab to complete 1 year of treatment as standard of care.

Subjects with undetectable ctDNA at study enrollment will receive standard of care durvalumab (10 mg/kg every 2 weeks, or equivalent, for 1 year). If subjects in Cohort 2 MRD progress prior to close of study, blood will be drawn for ctDNA testing.

Cohort 1 (1500 mg IV every 21 days, for 1 year), •Cohort 2 (10mg/kg every 2 weeks for 1 year)

Target area under the curve (AUC) not to exceed 750mg on Day 1 of every 21-day cycle

Cisplatin (75mg/m2 per institution guidelines) may be substituted for Carboplatin

not to exceed 75mg IV on Day 1 of every 21-day cycle

Rene Bonilla

Rene NH Bonilla

Maximilian Diehn, MD

The purpose of this study is to test whether or not number of circulating cancer cells detected in the blood can be decreased the by combining the standard treatment (durvalumab) with Tremelimumab and additional chemotherapy

Primary objective is to measure the change in the levels of circulating tumor DNA (ctDNA) in Cohort 1 (MRD+) due to the addition of Tremelimumab and platinum doublet chemotherapy in subjects with stage III unresectable disease with positive DNA treated with consolidation chemotherapy and immunotherapy.

Secondary Objectives:

To determine the proportion of subjects in Cohort 1 MRD+ for whom ctDNA becomes undetectable after adding chemotherapy and tremelimumab to consolidation durvalumab

To describe compare overall survival (OS) of subjects with baseline detectable ctDNA (Cohort 1 MRD+) vs baseline undetectable ctDNA (Cohort 2 MRD ) ·To compare progression free survival (PFS) between subjects with baseline detectable (Cohort 1 MRD+) vs baseline undetectable ctDNA (Cohort 2 MRD )

Personalized Escalation of Consolidation Treatment Following Chemoradiotherapy and Immunotherapy in Stage III NSCLC in Stage III NSCLC

Personalized Escalation of Consolidation Treatment Following Chemoradiotherapy and Immunotherapy in Stage III NSCLC

Participants in Cohort 1 MRD+ will be assessed for ctDNA levels at baseline and end of treatment, expected to be 4 cycles of 3 weeks per cycle (defined as ctDNA evaluable set or ctDES). The outcome will be assessed as the number of participants with a ≥ 3 fold decrease in ctDNA level, a number without dispersion.

Participants in Cohort 1 MRD+ will be assessed for ctDNA levels at baseline and end of treatment, expected to be 4 cycles of 3 weeks per cycle. The outcome will be assessed as the number of participants with or without detectable ctDNA, a number without dispersion.

Overall survival (OS) is defined as the period a participant remains alive after study registration until death due to any cause. Participants lost to follow up will be censored at last known date alive. The outcome will be reported as the number of participants in both cohorts remaining alive after 2 years, a number without dispersion.

Progression free survival (PFS) is defined as the period a participant remains alive without disease progression after study registration. Tumor status is assessed per the Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) by computed tomography (CT), positron emission tomography (PET) CT; and/or X rays. Participants lost to follow up will be censored at last known date alive. The outcome will be reported as the number of participants in both cohorts remaining alive without progression after 2 years, a number without dispersion.

* Complete Response (CR) = Disappearance of all lesions
* Partial Response (PR) = ≥30% decrease in the sum of the lesion diameters
* Overall Response (OR) = CR + PR
* Progressive disease (PD) = 20% increase in the sum of lesion diameters, and/or the appearance of 1+ new lesion(s)
* Stable disease (SD) = Small changes that do not meet any of the above criteria

Adverse events will be collected for participants of Cohort 1 (MRD+) who initiate treatment with durvalumab and tremelimumab through 930 days after the last dose of durvalumab. AE grade per the Common Terminology Criteria for Adverse Events (CTCAE v5) criteria and relationship to study treatment will be assessed. The outcome will be reported as the number of durvalumab and tremelimumab related adverse events by grade that Cohort 1 MRD+ participants experienced.

Maximilian Diehn

Vice Chair of Research, Division Chief of Radiation and Cancer Biology

Digestive System Diseases

Rare Diseases

Stomach Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

The blood samples for ctDNA and other tumor markers (such as CEA, et al.) will be first collected within 7 days before surgery, and then be tested after radical gastrectomy in scheduled interval.

AVENIO circulating tumor DNA (ctDNA) Analysis Kits is a portfolio of three next-generation sequencing (NGS) liquid biopsy assay kits for oncology research: the AVENIO ctDNA Targeted Kit, Expanded Kit and Surveillance Kit.

AVENIO ctDNA surveillance kit

Zhaoqing Tang, MD

This study is designed to evaluate the potential clinical utility of ctDNA in the field of gastric cancer treatment,especially the usage of an indicator of MRD(minimal residual disease) in post radical gastrectomy patients. The primary purpose of this trial is to demonstrate if the postoperative ctDNA analysis could be used as an indicator of MRD or adjuvant chemotherapy response in advanced gastric cancer after radical gastrectomy.The second purpose is to describe the profile of ctDNA in gastric cancer.

Gastric cancer is an important health problem, being the fifth most common cancer and the third leading cause of cancer related death worldwide.Incidence shows clear regional and sex variations-rates are highest in Eastern Asia, Eastern Europe, and South America and lowest in Northern and Southern Africa. In China, gastric cancer accounts for nearly 16% of all malignant tumors and more than 80% of gastric cancer are in advanced stage.

Minimal residual disease (MRD) was proposed to describe the remaining tumor cells after treatment with curative intent. For curable gastric cancer, MRD means residential cancer cells after radical gastrectomy which share phenotypic similarity and genetic heritage with the original tumor. Treating MRD can increase the rates of cure had been supported by the experience of using adjuvant therapy for some type of solid tumor (for example, colorectal cancer, breast cancer). The challenge in monitoring the MRD in gastric cancer patients is that there is no very sensitive method. Computed tomography(CT) and blood tumor markers are either difficult to detect peritonial dissemination, the most frequent recurrent pattern in gastric caner or with limited sensitivity and specificity.

Tumor-specific DNA mutations detected in the cell-free component of peripheral blood, which is known as circulating tumor DNA (ctDNA), in most patients, allow for the noninvasive molecular characterization detection of tumors, including genetic changes that are revealed by the selective pressure of adjuvant therapies. Considering the origin of ctDNA, it can be from different subclones of primary tumor or both primary and metastatic tumors, the ctDNA may overcome the problems caused by tumor heterogeneity. Additionally, the short half-life of ctDNA, about 2 hours, makes ctDNA an ideal dynamic marker of tumor bulk.

In summary, the ctDNA is a good candidate to be a new kind of blood tumor marker. The preliminary studies had shown very good prospects in some tumors, including breast caner and colon cancer.But little was known in gastric cancer, so we designed this study to demonstrate the potential clinical utility of ctDNA in the field of gastric cancer treatment, especially the usage of an indicator of MRD in post radical gastrectomy patients.

Potential Clinical Utilities of Circulating Tumor DNA in Gastric Cancer

Evaluating Potential Clinical Utilities of Circulating Tumor DNA in Gastric Cancer

Time is measured from first positive ctDNA detection to disease-free survival event.

For subjects with postoperative positive ctDNA, time is measured from first adjuvant chemotherapy to first negative ctDNA detection.

Time is measured between first positive ctDNA detection and first recurrence detected by conventional methods.

Profiling of the most frequently detected gene mutations and level of mutations in preoperative ctDNA.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Adjuvant ctDNA-Adapted Personalized Treatment in Early Stage NSCLC (ADAPT-E)	NCT04585477	Non-small Cell ... Non-small Cell ... Non-small Cell ... Non-small Cell ...	AVENIO ctDNA Su... Durvalumab	18 Years -	Stanford University
Personalized Escalation of Consolidation Treatment Following Chemoradiotherapy and Immunotherapy in Stage III NSCLC in Stage III NSCLC	NCT04585490	Non Small Cell ... NSCLC, Stage II... Nsclc	Durvalumab Carboplatin Pemetrexed Paclitaxel Cisplatin AVENIO ctDNA Su... Tremelimumab	18 Years -	Stanford University
Potential Clinical Utilities of Circulating Tumor DNA in Gastric Cancer	NCT04000425	Gastric Cancer	AVENIO ctDNA su...	18 Years - 75 Years	Shanghai Zhongshan Hospital
Potential Clinical Utilities of Circulating Tumor DNA in Gastric Cancer	NCT04000425	Gastric Cancer	AVENIO ctDNA su...	18 Years - 75 Years	Shanghai Zhongshan Hospital

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