ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation

Inclusion Criteria:

• Age > 18 years old AND

• Initial treatment is given with curative/radical intent AND

• Are planning to undergo regular follow-up and monitoring for cancer recurrence perstandard of care at the enrolling site AND

• Provided written informed consent to participate in the study AND

• Are willing to have de-identified clinical data shared with investigators at regularintervals as outlined in the study protocol and informed consent AND

• Are willing to provide blood samples at enrollment and at subsequent clinical visitscoinciding with standard of care follow-up, for up to 5 years as outlined in thestudy protocol and informed consent AND

• Have at least one Landmark blood sample

Have a histologically confirmed Index Cancer that qualifies for inclusion, defined as:

Primary Study Cohorts

• Cohort 1: Cohort 1: Muscle invasive carcinoma of the bladder, ureter, or renalpelvis (stage II-III),

• Cohort 2: Cohort 2: Non-small cell lung cancer (stage IB-III):

Cohort 2A: Resectable OR Cohort 2B: Unresectable,

• Cohort 3: Invasive breast carcinoma with hormone receptor (e.g. estrogen receptor (ER) and progesterone receptor (PR) expression) and human epidermal growth factorreceptor 2 (HER2) status known and one the following:

Cohort 3A: High-risk2 HER2+ breast cancer (any ER, PR status allowed) OR Cohort 3B: High-risk2 triple negative breast cancer (TNBC) OR Cohort 3C: High-risk3 HR-positive/HER2-negative invasive breast carcinoma,

• Cohort 4: Stage IIB-III cutaneous melanoma or limited (resectable) stage IV melanomatreated with curative intent,

• Cohort 5: Esophageal or gastroesophageal junction carcinoma (stage II-III),

• Cohort 6: Gastric adenocarcinoma (stage II-III),

• Cohort 7: Pancreatic adenocarcinoma that is has been surgically resected or iseligible for surgical resection,

• Cohort 8: Invasive squamous cell carcinoma of the head and neck (Includes stageI-IVB oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, nasal cavity, andparanasal sinus cancers),

• Cohort 9: High-risk epithelial ovarian or Fallopian tube carcinoma (Defined as FIGOstage IC-III or stage IA-IB that has high grade or clear cell histology),

• Cohort 10: High-risk endometrial carcinoma (Defined as 2023 FIGO Stage II-III),

• Cohort 11: High-risk renal cell carcinoma (Defined as high grade (grade 3-4) stageII, stage III or limited (resectable) stage IV treated with curative intent)

Exploratory Cohort

• Cohort 12: Pathologically confirmed adenocarcinoma of the rectum (located up to 15cm from the anal verge) that is undergoing or underwent a preoperative chemotherapy-or immunotherapy- containing regimen

Exclusion Criteria:

• History of allogeneic organ or tissue transplant

• Index cancer has predominantly neuroendocrine histology

• History of another primary cancer diagnosed within 3 years of enrollment, with theexception that in situ cancers, non-melanoma skin carcinomas, localized low- orintermediate risk prostate cancers, and stage I papillary thyroid carcinoma, andparticipants with bilateral/multifocal tumors within the same organ (for example,bilateral breast cancer) are allowed if diagnosed within 3 years of enrollment

• Known distant metastasis at time of enrollment (with the exception of participantswith limited/resectable stage IV cutaneous melanoma or RCC)