Clinical trial NCT04761783: BESPOKE Study of ctDNA Guided Immunotherapy
Official title: BESPOKE Study of ctDNA Guided Immunotherapy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Colorectal Cancer
Melanoma
Non-small Cell Lung Cancer
Keywords: BESPOKE
circulating tumor DNA
Lead sponsor: Natera, Inc.
Sponsor class: INDUSTRY
First posted: 2021-02-21
Enrollment: 290
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients who have been diagnosed with advanced colorectal cancer, non-small cell lung cancer, or melanoma

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.

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.

Eligibility 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

Primary outcomes:
measure: Examine the impact of SIGNATERA on treatment decisions on tumor assessment timepoints after initiation of immunotherapy
timeFrame: 2 years
Secondary outcomes:
measure: To determine progression free survival according to ctDNA change
timeFrame: 2 years
measure: Determine overall survival according to ctDNA change
timeFrame: 2 years
measure: Determine response rate according to ctDNA change in cases with progression of disease on first or second tumor assessment and who continue treatment.
timeFrame: 2 years
measure: To determine progression free survival according to ctDNA change in cases who achieve stable disease on first tumor assessment.
timeFrame: 2 years
measure: To determine duration of response according to ctDNA change in cases who achieve partial response or complete response as best overall response.
timeFrame: 2 years
measure: 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.
timeFrame: 2 years
measure: 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
timeFrame: 2 years
measure: Determine the impact of SIGNATERA in informing immunotherapy treatment decisions
timeFrame: 2 years
measure: Determine the impact of SIGNATERA on patient reported outcomes
timeFrame: 2 years
Other outcomes:
Locations:
city: San Carlos
country: United States
facility: Natera
state: California
Study officials:
affiliation: Natera, Inc.
name: Alexey Aleshin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.