VGH-TAYLOR: Comprehensive Precision Medicine Study Protocol on the Heterogeneity of Taiwanese Breast Cancer Patients

Figures & data

Figure 1. Flowchart of the study.

TMO comprehensive assay, Oncomine Comprehensive Assay v3; TMO cfDNA assay, Oncomine Breast cfDNA Assay; TMO IRR assay, Oncomine Immune Response Research Assay; TMO repertoire assay, Ion AmpliSeq Immune Repertoire Assay Plus-TCR beta.

^†Subjects with breast cancer recurrence at screening.

^‡Subjects who do not achieve pathological complete response (non-pCR), have breast cancer recurrence, and with paired tumor formalin-fixed paraffin-embedded tissues available.

^§Subjects who are currently receiving the first-line treatment for mBC and have PD within 3 months after initiating the first-line treatment for mBC (subjects with rapid PD).

BC: Breast cancer; mBC: Metastatic breast cancer; PD: Progressive disease; TMO: Thermo Fisher Oncomine; WGS: Whole-genome sequencing.

Table 1. Schedule of assessments for Group 1 subjects.

Group 1^† (surgery and adjuvant therapy setting)
Study activities	Unscheduled visit^‡	Visit 1^¶	Unscheduled visit^¶	Visit 2^¶	Visits 3–8^#	Unscheduled visit (confirmed diagnosis of recurrence)
		Before surgery		When adjuvant therapy completed	Every 6 months after visit 2
Blood collection for WGS (leukocytes)	X^§
FFPE tissues collection for WGS	X^§					X^§
FFPE tissues collection for TMO comprehensive assay	X		X			X^‡‡
Blood collection for TMO repertoire assay		X		X		X^‡‡
Fresh tissues collection for TMO IRR assay			X			X^‡‡
Blood collection for TMO circulating cell-free DNA assay		X		X	X^††	X^‡‡

† Subjects who are planning to receive surgery as the first-line treatment for breast cancer and followed by adjuvant therapy, or subjects with breast cancer recurrence at screening.

‡ This unscheduled visit could occur at screening and is only applicable for subjects with breast cancer recurrence at screening and enrolled in Group 1.

§ Only the paired FFPE tissues (primary and recurrent tumors) and blood samples collected from subjects with breast cancer recurrence at screening and enrolled in Group 1 will be used for WGS analysis.

¶ These visits (visit 1, unscheduled visit, and visit 2) are only applicable for subjects who are planning to receive surgery as the first-line treatment for breast cancer and followed by adjuvant therapy.

# These visits (visits 3–8) are only applicable for subjects with high risk of recurrence (i.e., with stage III breast cancer, TNBC or both HER2+ and lymph node-positive breast cancer).

†† For visits 3–8, blood samples will be collected at approximately 6, 12, 18, 24, 30 and 36 months after the completion of adjuvant therapy, respectively. If subjects have breast cancer recurrence within the 36-month period, the last time point for blood collection will be at the time when subjects are with confirmed diagnosis of recurrence.

‡‡ This sample collection will only occur when breast cancer recurrence is confirmed. The FFPE and fresh tumor tissues will be collected if available.

All scheduled visits for tissue and blood sample collection will follow the actual clinical practice. If the subject is not able to provide the tissue or blood sample at the specific time point during the study period or the samples collected failed the quality check process, it will not be considered as a protocol deviation.

FFPE: Formalin-fixed paraffin-embedded; IRR: Immune response research; TMO: Thermo Fisher Oncomine; WGS: Whole-genome sequencing.

Table 2. Schedule of assessments for Group 2 subjects.

Group 2^† (neoadjuvant therapy setting)
Study activities	Visit 1	Visit 2	Visits 3–8/14^¶	Unscheduled visit (confirmed diagnosis of recurrence)
	Before neoadjuvant therapy	When surgery is completed	Every 3 or 6 months after visit 2
Blood collection for WGS (leukocytes)		X^‡
FFPE tissues collection for WGS	X^‡	X^‡		X^‡
FFPE tissues collection for TMO comprehensive assay	X	X^§		X^††
Blood collection for TMO repertoire assay	X	X		X^††
Fresh tissues collection for TMO IRR assay	X	X		X^††
Blood collection for TMO circulating cell-free DNA assay	X	X	X^#	X^††

† Subjects who are planning to receive neoadjuvant therapy as the first-line treatment for breast cancer and followed by surgery.

‡ Only the paired FFPE tissues (primary and recurrent tumors) and blood samples collected from subjects who do not achieve pathological complete response (non-pCR) and with breast cancer recurrence will be used for WGS analysis.

§ FFPE tissues will only be collected from non-pCR subjects at visit 2.

¶ For pCR subjects, visits 3–8 will be applied. For non-pCR subjects, visits 3 to 14 will be applied.

# For pCR subjects, blood samples will be collected at approximately every 6 months after surgery (i.e., at 6, 12, 18, 24, 30 and 36 months). If subjects have breast cancer recurrence within the 36-month period, the last time point for blood collection will be at the time when subjects with confirmed diagnosis of breast tumor recurrence.

†† This sample collection will only occur when breast cancer recurrence is confirmed. The FFPE and fresh tumor tissues will be collected if available.

For non-pCR subjects, blood samples will be collected at approximately every 3 months after surgery (i.e., at 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33 and 36 months). If subjects have breast cancer recurrence within the 36-month period, the last time point for blood collection will be at the time when subjects with confirmed diagnosis of breast tumor recurrence.

All scheduled visits for tissue and blood sample collection will follow the actual clinical practice. If the subject is not able to provide the tissue or blood sample at the specific time point during the study period or the samples collected failed the quality check process, it will not be considered as a protocol deviation.

FFPE: Formalin-fixed paraffin-embedded; IRR: Immune response research; TMO: Thermo Fisher Oncomine; WGS: Whole-genome sequencing.

Table 3. Schedule of assessments for Group 3-1 subjects.

Group 3-1^† (de novo and treatment-naive stage IV breast cancer)
Study activities	Visit 1	Visit 2	Visits 3–14^‡	Unscheduled visit (confirmed diagnosis of first PD)
	Before receiving the first-line treatment for mBC	Achieve CR, PR or SD for at least 12 months after initiating first-line treatment for mBC	Every 3 months after visit 2
Blood collection for WGS (Leukocytes)	X
FFPE tissues collection for WGS	X			X^¶
FFPE tissues collection for TMO comprehensive assay	X			X^¶
Blood collection for TMO repertoire assay	X	X		X^¶
Fresh tissues collection for TMO IRR assay	X			X^¶
Blood collection for TMO circulating cell-free DNA assay	X	X	X^§	X^¶

† Subjects with de novo and treatment-naive stage IV breast cancer.

‡ These visits (visits 3–14) are only applicable for subjects who achieve CR, PR or SD for at least 12 months after initiating the first-line treatment for mBC.

§ For Visits 3 to 14, blood samples will be collected at approximately 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33 and 36 months after subjects achieve CR, PR, or SD for at least 12 months, respectively. If subjects have PD within the 36-month period, the last time point for blood collection will be at the time when subjects are with confirmed diagnosis of first PD.

¶ This sample collection will only occur when the first PD is confirmed. The FFPE and fresh tumor tissues will be collected if available.

All scheduled visits for tissue and blood sample collection will follow the actual clinical practice. If the subject is not able to provide the tissue or blood sample at the specific time point during the study period or the samples collected failed the quality check process, it will not be considered as a protocol deviation.

CR: Complete response; FFPE: Formalin-fixed paraffin-embedded; IRR: Immune response research; MBC: Metastatic breast cancer; PD: Progressive disease; PR: Partial response; SD: Stable disease; TMO: Thermo Fisher Oncomine; WGS: Whole-genome sequencing.

Table 4. Schedule of assessments for Group 3-2 subjects.

Group 3-2^† (stage IV breast cancer subjects with recurrence or posttreatment stage IV breast cancer subjects)
Study activities	Visit 1	Visit 2	Visits 3–14^‡	Unscheduled visit (confirmed diagnosis of first PD after enrollment)
	After enrollment/during current treatment	Achieve CR, PR or SD for at least 12 months after initiating the treatment for mBC	Every 3 months after visit 2
FFPE tissues collection for Thermo Fisher Oncomine (TMO) comprehensive assay	X			X^¶,^#
Blood collection for TMO repertoire assay	X	X		X^¶
Fresh tissues collection for TMO Immune Response Research (IRR) assay	X			X^¶
Blood collection for TMO circulating cell-free DNA assay	X	X	X^§	X^¶

† Subjects with stage IV breast cancer and meet any of the following conditions: subjects with breast cancer recurrence or subjects who had received or are currently receiving treatments for mBC.

‡ These visits (Visits 3–14) are only applicable for subjects who achieve CR, PR or SD for at least 12 months after initiating the treatment for mBC.

§ For visits 3–14, blood samples will be collected at approximately 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33 and 36 months after subjects achieve CR, PR or SD for at least 12 months, respectively. If subjects have PD within the 36-month period, the last time point for blood collection will be at the time when subjects are with confirmed diagnosis of first PD.

¶ This sample collection will only occur when the first PD is confirmed. The FFPE and fresh tumor tissues will be collected if available.

# For subjects who are currently receiving the first-line treatment for mBC and with PD less than 3 months, FFPE tumor tissues will be collected at every subsequent time when PD is confirmed until the last PD within the 3-year follow-up period.

All scheduled visits for tissue and blood sample collection will follow the actual clinical practice. If the subject is not able to provide the tissue or blood sample at the specific time point during the study period or the samples collected failed the quality check process, it will not be considered as a protocol deviation.

CR: Complete response; FFPE: Formalin-fixed paraffin-embedded; IRR: Immune response Research; MBC: Metastatic breast cancer; PD: Progressive disease; PR: Partial response; SD: Stable disease; TMO: Thermo Fisher Oncomine; WGS: Whole-genome sequencing.