Exploratory Platform Trial to Evaluate Immunotherapy Combinations With Chemotherapy for the Treatment of Patients With Previously Untreated Metastatic Pancreatic Adenocarcinoma

Core Inclusion Criteria

   1. Participant has histologically or cytologically documented diagnosis of pancreatic
   adenocarcinoma with metastatic disease. Participants with locally advanced disease are
   not eligible.

   a. Participants with recurrent locally advanced disease are eligible, provided: i. the
   last dose of chemotherapy and/or radiotherapy occurred > 4 months prior to the first
   dose of study intervention, and; ii. no systemic or radiotherapy has been administered
   in the metastatic setting.

   2. Participant must have measurable disease by RECIST v1.1.

   3. Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status
   of 0 or 1.

   4. A baseline tumor tissue sample is mandatory for enrollment. If archival tumor tissue
   is not available, then a fresh tumor biopsy must be provided.

   5. Participant must be age 18 years or older.

   6. Participant must have adequate organ function.

Core Exclusion Criteria

   1. Participant must not have received any prior treatment, including chemotherapy,
   biological therapy, or targeted therapy for mPDAC, with the following exceptions and
   notes:

      1. Participants who have received prior neoadjuvant or adjuvant therapy for
      pancreatic adenocarcinoma are eligible if neoadjuvant and adjuvant therapy
      (including chemotherapy and/or radiotherapy) was completed more than 4 months
      before the start of study intervention.

      2. Prior surgical resection is permitted.

      3. Participants who have received treatment with any other enadenotucirev-based
      therapy or anti-CD40 antibody at any time are not eligible for the study (cohort
      C only).

   2. Prior malignancy active within the previous 2 years except for locally curable cancers
   that have been apparently cured, such as basal or squamous cell skin cancer,
   superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.

   3. Participants with an active, known or suspected autoimmune disease. Participants with:
   type I diabetes mellitus; hypothyroidism only requiring hormone replacement; a history
   of Hashimoto syndrome, within 3 years of the first dose of study intervention, which
   resolved to hypothyroidism alone; skin disorders (such as vitiligo, psoriasis, or
   alopecia) not requiring systemic treatment; or conditions not expected to recur in the
   absence of an external trigger are permitted to enroll.