A Trial of Gemcitabine, Pembrolizumab and IMM-101 as First Line Treatment in Patients With Metastatic Pancreatic Cancer

Inclusion Criteria:

1. Patients aged > or = 18 years for age

2. Patient has given written informed consent to participate in the trial

3. Histologically or cytologically confirmed metastatic pancreatic ductaladenocarcinoma or its variants

4. Patient has been enrolled in the Precision-Panc Master Protocol and their tissue hasbeen deemed suitable for Next Generation Sequencing (NGS) analysis.

5. No prior systemic anti-cancer therapy for metastatic pancreatic cancer. Patients mayhave received prior pre-, peri-, or post-operative systemic anti-cancer therapy foroperable disease with curative intent provided that the last dose of systemicanti-cancer therapy was completed > 6 months before the recurrent disease wasdocumented

6. ECOG performance status 1, but not sufficiently fit to potentially toleratetreatment with a combination treatment regimen consisting of two or more cytotoxicchemotherapy agents in the opinion of the investigator.

7. Measurable disease by RECIST 1.1.

8. Estimated life expectancy > 3 months.

9. Adequate haematological and biochemical function.

10. Willingness to comply with study procedures including administration of studytherapies.

11. Females of childbearing potential must have a negative pregnancy test within 72hours of the first dose of study treatment and agree to use highly effectivecontraceptive measures during the study and for 6 months after the lastadministration of the study drug.

12. Male patients with partners of childbearing potential must agree to use highlyeffective contraceptive measures during the study and for 6 months after the lastadministration of the study drug

13. Patients with a history of Hepatitis C Virus (HCV) infection are eligible for thestudy if HCV viral load is undetectable at screening. Patients who have been treatedfor HCV infection must have completed curative anti-viral therapy at least 4 weeksbefore registration to the trial.

14. Patients who are hepatitis B positive will be eligible as long as they meet thefollowing criteria:

14.1. Patients who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks and have an undetectable HBV viral load before registration to the trial 14.2. Patients should remain on anti-viral therapy throughout study treatment and follow local guidelines for HBV anti-viral therapy post-completion of study treatment

Exclusion Criteria:

1. Pregnant or breast-feeding women.

2. Patients with cardiovascular disease defined as Stage II to IV congestive heartfailure (CHF) as determined by the New York Heart Association (NYHA) classificationsystem, or history of myocardial infarction (MI), or cardiac arrhythmia associatedwith haemodynamic instability, or unstable angina, or cerebral vascular accident, ortransient ischemia, if any have occurred within the previous 12 months prior tostudy treatment.

3. Any other serious medical or psychiatric disorder that would be, in the opinion ofthe investigator, a contra-indication to either the trial procedures or to therapywith gemcitabine, IMM-101 or pembrolizumab.

4. Any prior therapy with IMM-101 or an immune checkpoint inhibitor.

5. Major surgery within 28 days of starting study treatment and patients must haverecovered from any effects of major surgery.

6. Patients with a known hypersensitivity to gemcitabine, IMM-101, or pembrolizumab orany of the excipients of the products, including patients who have previouslyexperienced an allergic reaction to any mycobacterial product.

7. Current or prior use of immunosuppressive medication within 14 days before the firstdose of IMM-101 or pembrolizumab. The following are exceptions to this criterion:

7.1. Intranasal, inhaled, or topical steroids; or local steroid injections (e.g.,intra-articular injection) 7.2. Systemic corticosteroids at physiologic doses not toexceed 10 mg/day of prednisolone or equivalent 7.3. Steroids as premedication forhypersensitivity reactions (e.g., CT scan premedication) and chemotherapy-inducednausea and vomiting

8. History of allogenic organ transplant.

9. Previous severe or life-threatening skin adverse reaction with otherimmune-stimulatory anticancer agents.

10. Active autoimmune disorders, or prior documented severe autoimmune or inflammatorydisorders requiring immunosuppressive treatment in the last 2 years (includinginflammatory bowel disease [e.g., colitis, Crohn's disease], diverticulitis with theexception of diverticulosis, coeliac disease, irritable bowel syndrome, or otherserious gastrointestinal chronic conditions associated with diarrhoea); systemiclupus erythematosus; Wegener syndrome (granulomatosis with polyangiitis), Graves'disease; rheumatoid arthritis, hypophysitis, uveitis or other evidenced autoimmunedisorders. The following are exceptions to this criterion:

10.1. Patients with vitiligo or alopecia 10.2. Diabetes mellitus type I or resolvedchildhood asthma/atopy 10.3. Patients with hypothyroidism (e.g., following Hashimotosyndrome) stable on hormone replacement 10.4. Any chronic skin condition that doesnot require systemic therapy 10.5. Patients with coeliac disease controlled by dietalone

11. History of (non-infectious) interstitial lung disease or pneumonitis that requiredsteroids or current pneumonitis.

12. Patients with an active infection requiring systemic therapy.

13. Concurrent active Hepatitis B (defined as HBsAG positive and/or detectable HBV/DNA)or Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA)infection.

14. History of (non-infectious) interstitial lung disease or pneumonitis that requiredsteroids or current pneumonitis.

15. Patients with an active infection requiring systemic therapy.

16. Receipt of the last dose of an approved (marketed) anticancer therapy (chemotherapy,targeted therapy, biologic therapy, monoclonal antibodies, etc.) or radiotherapywithin 28 days or 5 half-lives, whichever is the longest, prior to the first dose ofstudy treatment.

17. Received prior radiotherapy within 2 weeks of the start of the study intervention.Participants must have recovered from all radiation-related toxicities, not requirecorticosteroids, and not have had radiation pneumonitis. A 1-week washout ispermitted for palliative radiation (≤2 weeks of radiotherapy) to non-Central NervousSystem (CNS) disease.

18. Other malignancy within 3 years except for non-invasive malignancies such ascervical carcinoma in situ, non-melanoma carcinoma of the skin, or ductal carcinomain situ of the breast that has/have been surgically cured ortreated/biochemically-stable, organ-confined prostate cancer (patients can remain ontreatment for this indication as long as not contraindicated with study treatment).

19. Receipt of a live attenuated vaccine within 30 days prior to the first dose of studyth