Chemotherapy With Nab-paclitaxel/Germcitabine/Cisplatin +/- BGB324 With Pancreatic Cancer

Bemcentinib inhibits pancreatic cancer proliferation as monotherapy and in combination with
gemcitabine through inhibition of the Axl pathway. The combination of
nab-paclitaxel/gemcitabine/cisplatin has encouraging signs of clinical activity in patients
with metastatic pancreatic cancer38. We would like to build on this combination in a
biomarker driven phase 1b/2 clinical trial of bemcentinib in
nab-paclitaxel/gemcitabine/cisplatin for patients with metastatic pancreatic cancer.

Inclusion Criteria:

1. Ability to understand and the willingness to sign a written informed consent.

2. Patients must have a histologically or cytologically confirmed pancreatic
adenocarcinoma that is metastaticor recurrent.

3. No prior systemic therapy for metastatic or recurrent disease.

- Prior adjuvant gemcitabine, if completed more than 12 months prior to date of
enrollment, is acceptable.

- Radiosensitizing chemotherapy, if completed at least 4 weeks from date of
enrollment, is acceptable.

4. Measurable disease is required per RECIST1.1 criteria.

5. Age 18-70 years at the time of enrollment.

7. ECOG performance status 0 or 1. 8. Have resolution of toxic effect(s) of the most recent
prior chemotherapy to Grade 1 or less (except alopecia). If the patient received major
surgery or radiation therapy of >30 Gy, they must have recovered from the toxicity and/or
complications from the intervention.

9. Adequate hematologic, hepatic, and renal function. All screening labs should be
performed within 14 days of registration.

10. Female patients of childbearing potential must have a negative pregnancy test (either
urine or serum pregnancy test) within 72 hours prior to the first dose of study treatment.
If the urine pregnancy test is positive or cannot be confirmed as negative, a serum
pregnancy test will be required. A female of child-bearing potential is any woman
(regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate
by choice) who meets the following criteria:

- Has not undergone a hysterectomy or bilateral oophorectomy; or

- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has
had menses at any time in the preceding 12 consecutive months).

11. Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, for
the duration of study participation, and for 120 days following completion of therapy.
Should a woman become pregnant or suspect she is pregnant while participating in this
study, she should inform her treating physician immediately.

Exclusion Criteria:

1. Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 4 weeks of the first dose of study treatment.

2. Patients with known untreated brain metastases. Patients without known brain
metastases do not require radiologic imaging prior to enrollment.

3. Has a known additional malignancy that is progressing or requires active treatment.
Note: Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of
the skin that has undergone potentially curative therapy or in situ cervical cancer.

4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, significant pulmonary disease (shortness of breath at rest or mild
exertion), or uncontrolled infection or psychiatric illness/social situations that
would limit compliance with study requirements.

5. History of the following cardiac conditions:

1. Congestive cardiac failure of >Grade II severity according to the NYHA (defined
as symptomatic at less than ordinary levels of activity);

2. Ischemic cardiac event including myocardial infarction within 3 months prior to
date of enrollment

3. Uncontrolled cardiac disease, including unstable angina pectoris, uncontrolled
hypertension (i.e. sustained systolic BP >160 mmHg or diastolic BP >90 mmHg),
cardiac arrhythmia, or need to change medication due to lack of disease control
within 6 weeks prior to date of enrollment;

4. History or presence of sustained bradycardia (≤55 BPM), left bundle branch block,
cardiac pacemaker or ventricular arrhythmia. Note: Patients with a
supraventricular arrhythmia requiring medical treatment, but with a normal
ventricular rate are eligible;

5. Known family history or personal history of long QTc syndrome or previous
drug-induced QTc prolongation of at least Grade 3 (QTc >500 ms).

6. Abnormal left ventricular ejection fraction (LVEF) on echocardiography or MUGA (less
than the lower limit of normal for a patient of that age at the treating institution
or <45%).

7. Current treatment with any agent known to cause Torsades de Pointes which cannot be
discontinued at least five half-lives or two weeks prior to the first dose of study
treatment.

8. Screening 12-lead ECG with a measurable QTc interval according to Fridericia's
correction >450 ms.

9. Known active infection with human immunodeficiency virus (HIV), hepatitis B or C
viruses (screening not required, follow institutional practice):

1. Patients who have a history of hepatitis B infection are eligible provided they
are hepatitis B surface antigen negative.

2. Patients who have a history of hepatitis C infection are eligible provided they
have no evidence of hepatitis C ribonucleic acid using a quantitative polymerase
chain reaction assay at least 6 months after completing treatment for hepatitis C
infection.

10. Active, clinically significant serious infection requiring treatment with antibiotics,
anti-virals or anti-fungals.

11. Treatment with any medication which is predominantly metabolized by CYP3A4 and has a
narrow therapeutic index.

12. Major surgery within 4 weeks prior to date of enrollment; excluding skin biopsies and
procedures for insertion of central venous access devices.

13. Inability to tolerate oral medication.

14. Existing gastrointestinal disease affecting drug absorption such as celiac disease or
Crohn's disease, or previous bowel resection which is considered to be clinically
significant or could interfere with absorption.

15. Known lactose intolerance.

16. Treatment with any of the following: histamine receptor 2 inhibitors, proton pump
inhibitors or antacids within 7 days of start of study treatment.

17. Continuous treatment with more than 40 mg prednisolone (or equivalent dose of systemic
corticosteroid) which cannot be discontinued up to one week prior to starting
bemcentinib.

18. Is pregnant or breastfeeding.

19. Any significant medical condition lab abnormality, or psychiatric illness, in the
opinion of the investigator, that might interfere with the patient's participation in
the study or in the evaluation of the study results.

20. Unwillingness or inability to comply with study procedures.