Inclusion Criteria:

Phase 1 or 2

1. Histologically or cytologically confirmed metastatic or unresectable locally
advanced, recurrent NSCLC

2. Documented evidence of any activating mutation in the EGFR determined by either
sequencing or PCR-based testing of the tumor tissue using local laboratory technique

3. Have undergone biopsy of either primary or metastatic tumor tissue within 28 days of
dosing study drug and have tissue available to send to sponsor lab or are able to
undergo a biopsy during screening

4. Life expectancy of at least 3 months

5. ECOG performance status of 0 to 1

6. Age ≥ 18 years

7. Adequate hematological and biological function

8. Written consent on an Institutional Review Board/Independent Ethics
Committee-approved Informed Consent Form prior to any study-specific evaluation

Patients enrolling into Phase 1 must also meet the following criteria:

1. Prior treatment with EGFR-directed therapy (eg. erlotinib, gefitinib, neratinib,
afatinib, or dacomitinib [PF299804]) Prior chemotherapy, including intervening
chemotherapy, is allowed.

- The washout period for a reversible EGFR inhibitor (erlotinib, gefitinib) is a
minimum of 5 days.

- The washout period for an irreversible EGFR inhibitor (neratinib, afatinib,
dacomitinib) is a minimum of 14 days.

- The washout period for chemotherapy is a minimum of 14 days.

- Any toxicity related to prior treatment must have resolved to Grade 1 or less.

2. Be willing and able to eat a high-fat breakfast on Day 1 of the study (only
applicable to food-effect cohort).

Patients enrolling into Phase 2 must also meet the following criteria:

1. Disease progression while on treatment with EGFR-directed therapy (e.g. erlotinib,
gefitinib, neratinib, afatinib, or dacomitinib [PF299804]) with no intervening
treatment allowed after most recent EGFR-directed therapy. Prior chemotherapy is
allowed as long as the most recent treatment was an EGFR-directed therapy.

- The washout period for a reversible EGFR inhibitor (erlotinib, gefitinib) is a
minimum of 5 days.

- The washout period for an irreversible EGFR inhibitor (neratinib, afatinib,
dacomitinib) is a minimum of 14 days.

- Any toxicity related to prior EGFR inhibitor treatment must have resolved to
Grade 1 or less.

2. Documented evidence of T790M mutation in EGFR as determined by PCR-based testing of
tumor tissue using sponsor central lab following disease progression on most recent
prior EGFR-directed therapy.

3. Measurable disease according to RECIST Version 1.1.

Exclusion Criteria:

1. History of prior malignancy except:

- Curatively treated non-melanoma skin cancer

- Curatively treated in-situ cervical cancer

- Incidental histologic finding of prostate cancer (tumor/node/metastasis [TNM]
stage of T1a or T1b)

2. History of interstitial lung disease related to prior EGFR inhibitor therapy

3. Symptomatic brain metastases

4. Treatment with prohibited medications (e.g., concurrent anticancer therapy including
other chemotherapy, radiation [except palliative radiation therapy on non-target
lesions for patients without progression], hormonal treatment [except corticosteroids
and megestrol acetate], or immunotherapy) ≤14 days prior to treatment with CO-1686

5. Prior treatment with CO-1686

6. Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's
method (QTcF) >450 msec (males) or >470 msec (females), PR >240 msec, or QRS >110
msec

7. Family history of long QT syndrome

8. Implantable pacemaker or implantable cardioverter defibrillator

9. For phase 1 patients, treatment with any medication known to produce QT prolongation

10. Non-study related surgical procedures ≤14 days prior to administration of CO-1686.
In all cases, the patient must be sufficiently recovered and stable before treatment
administration.

11. Females who are pregnant or breastfeeding

12. Refusal to use adequate contraception for fertile patients (females and males) for 6
months after the last dose of CO-1686

13. Presence of any serious or unstable concomitant systemic disorder incompatible with
the clinical study (e.g., substance abuse, uncontrolled psychiatric condition,
uncontrolled intercurrent illness including active infection, arterial thrombosis,
and symptomatic pulmonary embolism)

14. Any other reason the investigator considers the patient should not participate in the
study