BESPOKE Study of ctDNA Guided Immunotherapy

• ClinicalTrials.gov Identifier: NCT04761783
• Recruitment Status: Recruiting
• First Posted: February 21, 2021
• Last Update Posted: February 6, 2023
• Sponsor: Natera, Inc.
• Information provided by (Responsible Party): Natera, Inc.

Study Description

Brief Summary:

This is a prospective data collection study of patients with advanced solid tumors who will receive standard of care immunotherapy (IO) and will be monitored with SIGNATERA™ testing. SIGNATERA™ test will be performed at baseline and during routine care. The test results will be part of assessing tumor response. The correlation between SIGNATERA™ test results and subsequent treatment decisions will be examined to compare actual treatment delivered against treatment decisions potentially impacted by SIGNATERA™ results. Treatment administered, tumor assessment results, time to progression, overall survival, physician questionnaires, and patient-reported outcomes will be collected/recorded.

Condition or disease
Colorectal Cancer; Melanoma; Non-small Cell Lung Cancer

Detailed Description:

Primary Objective:

● To examine the impact of SIGNATERA™ on clinical decision-making regarding continuation, discontinuation, escalation, or de-escalation of immunotherapy.

Secondary Objective:

● To prospectively evaluate the utility of SIGNATERA™ as a tool to detect early evidence of response or progression in patients with advanced solid tumors receiving immune checkpoint inhibitors.

Study Design

• Study Type: Observational
• Estimated Enrollment: 1539 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: BESPOKE Study of ctDNA Guided Immunotherapy
• Actual Study Start Date: May 28, 2021
• Estimated Primary Completion Date: May 2025
• Estimated Study Completion Date: May 2025

Groups and Cohorts

Group/Cohort
Prospective arm; Patients will receive SIGNATERA™ test results and the immunotherapy treatment regimen, dosing schedule, duration of treatment, number of cycles, and modifications during treatment will be at the discretion of the HCP. Patients will be followed for up to two years with periodic whole blood collection. Treatment administered, disease-free survival, overall survival, time to recurrence, physician questionnaires and patient-reported outcomes will be recorded.
Control arm; Control cases must have undergone immunotherapy treatment and have follow-up data available in their medical record at the participating site for two years following initiation of immunotherapy or death.

Outcome Measures

Primary Outcome Measures :

1. Examine the impact of SIGNATERA on treatment decisions on tumor assessment timepoints after initiation of immunotherapy [ Time Frame: 2 years ]
   Percent of patients who have their immunotherapy treatment regimen changed due to post-treatment SIGNATERA ctDNA test result

Secondary Outcome Measures :

1. To determine progression free survival according to ctDNA change [ Time Frame: 2 years ]
   Compare progression free survival, defined as the duration of time between enrollment and an increase in severity of disease as determined by patient's treating physician, between groups determined by change in ctDNA
2. Determine overall survival according to ctDNA change [ Time Frame: 2 years ]
   Compare overall survival, defined as the duration of time between enrollment and death for any reason, between groups determined by change in ctDNA
3. Determine response rate according to ctDNA change in cases with progression of disease on first or second tumor assessment and who continue treatment. [ Time Frame: 2 years ]
   Compare percentage of patients that experience partial or complete response during the study, between groups determined by change in ctDNA
4. To determine progression free survival according to ctDNA change in cases who achieve stable disease on first tumor assessment. [ Time Frame: 2 years ]
   Compare progression free survival between groups determined by change in ctDNA
5. To determine duration of response according to ctDNA change in cases who achieve partial response or complete response as best overall response. [ Time Frame: 2 years ]
   Compare duration of response, defined as the length of time from initial response to disease progression, between groups determined by change in ctDNA
6. To determine percentage of patients with at least 6 months of durable clinical response according to ctDNA change in patients who achieve at least partial response on best tumor assessment. [ Time Frame: 2 years ]
   Among all patients that are clinically identified to experience partial or complete response, percentage that have at least 6 months durable clinical response as determined by ctDNA change
7. Determine the impact of SIGNATERA on the confidence in immunotherapy treatment decisions based on the number of patients in which treating physician reports SIGNATERA made them more confident in immunotherapy treatment regimen [ Time Frame: 2 years ]
   Percent of patients whose treating physician reported that SIGNATERA result made them more confident in selected immunotherapy treatment regimen
8. Determine the impact of SIGNATERA in informing immunotherapy treatment decisions [ Time Frame: 2 years ]
   Percent of patients whose immunotherapy treatment regimen was changed as a result of SIGNATERA and/or whose treating physician reported that SIGNATERA result made them more confident in selected immunotherapy treatment regimen
9. Determine the impact of SIGNATERA on patient reported outcomes [ Time Frame: 2 years ]

   Assess patient anxiety levels and wellbeing in patients receiving SIGNATERA ctDNA test results.

   Patient responses to patient reported outcome questionnaires:

   EORTC QLQ-C30

   Assess if SIGNATERA makes patients feel that they are receiving the right treatment and determine if patients will continue to use Signatera in the future to monitor their cancer.

Biospecimen Retention:   Samples With DNA

There are two arms to this study: A prospective arm that will enroll 1539 patients, and a historical control (retrospective arm) that will enroll 513 patients.

Each participant in the Prospective arm will have received the commercially available SIGNATERA™ test.

Subjects prospectively enrolled and whom consent to "Optional future Research" may have bio-specimens stored for future research. The historical arm (retrospective cohort) will not have any bio-specimens collected or stored.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

Patients who have been diagnosed with advanced colorectal cancer, non-small cell lung cancer, or melanoma

Criteria

Prospective Inclusion Criteria:

1. Male or female patients 18 years of age or older at the time of signing informed consent form (ICF)

2. Any patient with documented metastatic or locally advanced, unresectable cancer of the types within the following cohorts:

   1. Melanoma
   2. Non-small cell lung cancer
   3. Colorectal cancer

3. Patients must be clinically eligible and planned to receive therapy with an anti-neoplastic agent that works by immune checkpoint blockade, anti-PD-1, anti-CTLA-4, or anti-PD-L1:

   1. Pembrolizumab (Keytruda)
   2. Nivolumab (Opdivo)
   3. Ipilimumab (Yervoy)
   4. Durvalumab (Imfinzi)
   5. Cemiplimab (Libtayo)
   6. Atezolizumab (Tecentriq)
   7. Avelumab (Bavencio)
4. Patients must have measurable disease according to RECIST criteria, and at least one lesion that can be accurately measured in at least one dimension as >10 mm.
5. Patients must be able to follow study visit schedule and willing to provide up to 20 mL of peripheral blood samples at the indicated time points
6. ECOG Performance status 0,1, or 2
7. Able to read, understand and provide written informed consent
8. Willing and able to comply with the study requirements
9. Selected by their HCP to receive SIGNATERA testing according to the current evidence-informed schedule as part of their routine of practice

Prospective Exclusion Criteria:

1. Female patients that are pregnant
2. History of bone marrow or organ transplant
3. Medical condition that would place the patient at risk as a result of blood donation, such as bleeding disorder
4. Serious medical condition that may adversely affect ability to participate in the study
5. Has initiated Immunotherapy

Control Arm Inclusion Criteria:

1. Male or female patients 18 years of age or older at the time of signing informed consent form (ICF)

2. Any patient with documented metastatic or locally advanced, unresectable cancer of the types within the following cohorts:

   1. Melanoma
   2. Non-small cell lung cancer
   3. Colorectal cancer

3. Patients must be clinically eligible and planned to receive therapy with an anti-neoplastic agent that works by immune checkpoint blockade, anti-PD-1, anti-CTLA-4, or anti-PD-L1:

   1. Pembrolizumab (Keytruda)
   2. Nivolumab (Opdivo)
   3. Ipilimumab (Yervoy)
   4. Durvalumab (Imfinzi)
   5. Cemiplimab (Libtayo)
   6. Atezolizumab (Tecentriq)
   7. Avelumab (Bavencio)
4. Patients must have measurable disease according to RECIST criteria, and at least one lesion that can be accurately measured in at least one dimension as >10 mm.
5. Patients must be able to follow study visit schedule and willing to provide up to 20 mL of peripheral blood samples at the indicated time points
6. ECOG Performance status 0,1, or 2
7. Able to read, understand and provide written informed consent
8. Willing and able to comply with the study requirements
9. Selected by their HCP to receive SIGNATERA testing according to the current evidence-informed schedule as part of their routine of practice

Control Arm Exclusion Criteria:

1. Female patients that are pregnant
2. History of bone marrow or organ transplant
3. Medical condition that would place the patient at risk as a result of blood donation, such as bleeding disorder
4. Serious medical condition that may adversely affect ability to participate in the study
5. Has initiated Immunotherapy

Contacts and Locations

Contacts

Contact: Kayla Gelow; 650-249-9091; kgelow@natera.com

Locations

United States, California

Natera; Recruiting

San Carlos, California, United States, 94070

Sponsors and Collaborators

Natera, Inc.

Investigators

• Principal Investigator: Alexey Aleshin, MD; Natera, Inc.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kasi PM, Chakrabarti S, Sawyer S, Krainock M, Poklepovic A, Ansstas G, Maninder M, Malhotra M, Ensor J, Gao L, Eroglu Z, Ellers S, Billings P, Rodriguez A, Aleshin A. BESPOKE IO protocol: a multicentre, prospective observational study evaluating the utility of ctDNA in guiding immunotherapy in patients with advanced solid tumours. BMJ Open. 2022 May 30;12(5):e060342. doi: 10.1136/bmjopen-2021-060342.

• Responsible Party: Natera, Inc.
• ClinicalTrials.gov Identifier: NCT04761783
• Other Study ID Numbers: 20-043-NCP
• First Posted: February 21, 2021
• Last Update Posted: February 6, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Natera, Inc.:

BESPOKE; circulating tumor DNA

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases