Development and Validation of a cfDNA Assay for Predicting Early Non-response to Therapy in Metastatic Cancer

Most anticancer drugs are effective only in subgroups of patients, and our current
understanding of tumor biology does not allow us to predict accurately which patient will
benefit from a specific therapeutic regimen. The definitive proof of the effectiveness of a
therapy is improvement in clinical symptoms and survival. Imaging is generally used to assess
therapeutic effects earlier and more objectively. Current response assessment is based
primarily on changes in tumor size as measured by CT or other anatomic imaging modalities.

Cadex Genomics has developed an analytically validated cell-free DNA (cfDNA) quantitative
real-time polymerase chain reaction (qPCR) assay that utilizes standard qPCR platforms for
processing, this test can reliably obtain results from small blood volumes and possesses
exceptionally high analytical sensitivity of circulating cfDNA.

The purpose of this study is to accrue samples for the further development and clinical
validation of a blood-based cell-free cfDNA qPCR assay as a potential biomarker for early
non-response to therapy in stage IV non-small cell lung cancer (NSCLC) and colorectal cancer
(CRC).

Inclusion Criteria:

1. Age ≥ 18 years.

2. Documented stage IV NSCLC or CRC (can be new diagnosis, persistent or recurrent
disease).

3. Planned initiation of new systemic first- or second-line treatment or subsequent
therapies with chemotherapy, immunotherapy, targeted therapy or combination thereof.

4. Measurable disease with CAT Scan (CT) or MRI or PET/CT monitoring pre-therapy and
planned CT or MRI or PET/CT monitoring for treatment response.

5. Willing and able to donate up to 30mL of blood via venipuncture.

6. Willing and able to provide informed consent.

Exclusion Criteria:

1. No documentation of stage IV NSCLC or CRC.

2. Systemic treatment is not planned.

3. Baseline tumor measurements are not available .

4. CT or MRI or PET/CT monitoring for treatment response is not planned within 8-12 weeks

5. Presence of active autoimmune disease on active therapy.

6. Patients must have no history of DVT, PE, sepsis within the prior 2 weeks or have
recovered from any other serious illness

7. Patient has received any doses of the new block of therapy before the first designated
blood draw.

8. Performance status ECOG 3 or 4, not secondary to the tumor, at time of either blood
draw.

9. No evidence of acute renal failure.