The ASCEND Study: Gemcitabine and Nab-Paclitaxel With LSTA1 (Certepetide) or Placebo in Patients With Untreated Metastatic Pancreatic Ductal Adenocarcinoma

Inclusion Criteria:

• Adults, 18 years or older with histologically confirmed metastatic pancreatic ductaladenocarcinoma or poorly differentiated carcinoma.

• Measurable disease according to RECIST 1.1.

• Archival tumour tissue for tertiary correlative studies (biopsy or resection ofprimary or metastasis). Fine needle aspirate (FNA) or brushings will not beaccepted.

• ECOG performance of 0-1 (Appendix 2)

• Adequate renal and haematological function

• Adequate hepatic function, defined as:

Bilirubin <1.5 X ULN (Upper Limit of Normal), AST or ALT ≤ 5x ULN. If a person was recently stented with improving bilirubin, the person can be randomised with bilirubin up to 3 x ULN provided chemotherapy is not administered until within the stated thresholds.

• Willing and able to comply with all study requirements, including treatment, timingand/or nature of required assessments.

• Study treatment both planned and able to start within 7 days after randomisation

• Signed, written informed consent.

Exclusion Criteria:

• Uncontrolled metastatic disease to the central nervous system. To be eligible, knownCNS metastases should have been treated with surgery and/or radiotherapy and thepatient should have been receiving a stable dose of steroids for at least 2 weeksprior to randomisation, with no deterioration in neurological symptoms during thistime.

• Prior chemotherapy or investigational anti-cancer therapy for metastatic pancreaticadenocarcinoma. Prior treatments with curative intent or for locally advanceddisease are allowed, provided the last dose of chemotherapy was administered morethan 6 months prior to randomisation.

• Prior radiotherapy or major surgery (as defined by local investigator) within 14days of starting treatment.

• Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anti-cancer therapy withthe exception of alopecia, vitiligo and the laboratory values defined in theinclusion criteria. Participants with Grade ≥2 peripheral neuropathy are notallowed.

• Concurrent use of any other anti-cancer therapy including chemotherapy, targetedtherapy, immunotherapy or biological agents.

• Known allergy or hypersensitivity to any of the study drugs and excipients.

• Any significant active infection, including chronic active hepatitis B, hepatitis C,or HIV. Participants with known Hepatitis B/C infection will be allowed toparticipate providing evidence of viral suppression has been documented and thepatient remains on appropriate anti-viral therapy.

• History of prior or synchronous malignancy within 2 years prior to randomisation,except:

1. Malignancy that was treated with curative intent and for which there has beenno known active disease for ≥2 years prior to randomisation.

2. Curatively treated non-melanoma skin cancer, cervical cancer in situ,superficial transitional cell carcinoma of the bladder, stage 1 endometrialcarcinoma, prostatic intraepithelial neoplasia, low-grade papillary thyroidcancer, untreated localised very low risk or low risk prostate cancer underobservation.

• Concurrent illness, including severe infection that may jeopardise the ability ofthe person to undergo the procedures outlined in this protocol with reasonablesafety.

• Neuroendocrine pancreatic carcinoma.

• Life expectancy of less than 3 months.

• Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal,infertile, or use a reliable means of contraception. Women of childbearing potentialmust have a negative pregnancy test done within 7 days prior to randomisation. Menmust use a reliable means of contraception.

• Serious medical or psychiatric conditions that might limit the ability of the personto comply with the protocol.