Safety and Efficacy of Combination Listeria/GVAX Pancreas Vaccine in the Pancreatic Cancer Setting

• GVAX Pancreas Vaccine (Biological), also known as GVAX
• CRS-207 (Biological)
• Chemotherapy (Drug): Investigator's choice of one of the following commercially available products: gemcitabine; capecitabine; fluorouracil with or without leucovorin; irinotecan; or erlotinib.
• cyclophosphamide (Drug), also known as Cytoxan

Primary outcomes

• Primary Cohort: Overall Survival (OS) Censored at 138 Deaths (ITT Set) [Subjects were followed from date of randomization to the date of death by any cause, whichever came first, assessed up to 32 months. Analysis conducted when 138 deaths reached in the Primary Cohort in the FAS.]: OS was estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CIs), with censoring at the date when 138 deaths were reached in the Primary Cohort in the FAS. Subjects without documentation of death at the time of final analysis were censored as of the date the subject was last known to be alive on/prior to the primary analysis data cut.
• Primary Cohort: OS (All Data, FAS) [Subjects followed for survival from date of randomization until lost to follow-up, withdrawal of consent, or death, whichever came first, assessed up to 32 months.]: For all treated subjects, OS was calculated using KM methods with 95% CIs. Subjects without documentation of death at the time of the analysis were censored as of the date the subject was last known to be alive on/prior to the final analysis data cut.
• 2nd-line Cohort: OS (All Data, FAS) [Subjects followed for survival from date of randomization until lost to follow-up, withdrawal of consent, or death, whichever came first, assessed up to 32 months.]: For all treated subjects, OS was calculated using KM methods with 70% CIs. Subjects without documentation of death at the time of the analysis were censored as of the date the subject was last known to be alive on/prior to the final analysis cut. 70% CIs were selected to provide an 80% probability to rule out differences in median survival less than -2.4 months between the 2nd-line Cohort: Chemotherapy arm and the 2nd-line Cohort: Cy/GVAX + CRS-207 and 2nd-line Cohort: CRS-207 arms, based upon the assumptions made in the statistical analysis plan (SAP).

Secondary outcomes

• Number of Participants With Adverse Events in Each Treatment Arm Treatment Regimen [From the start of the first study drug administration on Day 1, Week 1, through 28 days after the last study drug dose, assessed up to 32 months from the date of randomization.]: Safety was assessed based upon the number of adverse events (AEs) that occurred in the FAS of each treatment arm, including serious AEs and total AEs. Total AEs included both serious and non-serious AEs.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Have histologically proven malignant adenocarcinoma of the pancreas; measurable disease is not required, mixed histology is not allowed; subjects must have metastatic disease
* 2nd line, 3rd line or greater
* At least 18 years of age
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Anticipated life expectancy >12 weeks
* For women and men of childbearing potential, a medically acceptable method of highly effective contraception (oral hormonal contraceptive, condom plus spermicide, or hormone implants) must be used throughout the study period and for 28 days after their final vaccine administration. A barrier method of contraception must be employed by all subjects (male and female), regardless of other methods.
* Have adequate organ function as defined by specified laboratory values

Exclusion Criteria:

* Allergy to both penicillin \& sulfa or suspected hypersensitivity to granulocyte-macrophage colony stimulating factor (GM-CSF), dimethyl sulfoxide, fetal bovine serum, trypsin, yeast, glycerol or other component of the therapy options
* Known history or evidence of brain metastases, immunodeficiency disease or immunocompromised state or history of autoimmune disease requiring systemic steroids or other immunosuppressive treatment
* Have any evidence of hepatic cirrhosis or clinical or radiographic ascites
* Have prosthetic heart valves, major implant or device placed in the last 12 months or history of infection with implant/device that cannot be easily removed
* Rapidly progressing disease
* Clinically significant and/or malignant pleural effusion
* Received prior GVAX pancreas vaccine or CRS-207
* Major surgery or significant traumatic injury (or unhealed surgical wounds) occurring within 28 days prior to receiving study drug, or planned surgery requiring general anesthesia
* Infection with HIV or hepatitis B or C at screening
* Valvular heart disease that requires antibiotic prophylaxis for prevention of endocarditis
* Pregnant or breastfeeding
* Unable to avoid close contact with another individual known to be at high risk of listeriosis (e.g., newborn infant, pregnant woman, HIV-positive individual) during the course of CRS-207 treatment until completion of antibiotic regimen
* Conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures

Participant flow

Outcome results

• Primary Cohort: Overall Survival (OS) Censored at 138 Deaths (ITT Set) (Primary), Median, months: Primary Cohort: Cy/GVAX + CRS-207 3.8 (2.9 to 5.3); Primary Cohort: CRS-207 5.4 (4.2 to 6.9); Primary Cohort: Chemotherapy 4.6 (4.2 to 5.8)
• Primary Cohort: OS (All Data, FAS) (Primary), Median, months: Primary Cohort: Cy/GVAX + CRS-207 4.2 (3.0 to 5.4); Primary Cohort: CRS-207 5.2 (4.2 to 6.3); Primary Cohort: Chemotherapy 4.7 (3.8 to 6.0)
• 2nd-line Cohort: OS (All Data, FAS) (Primary), Median, months: 2nd-line Cohort: Cy/GVAX + CRS-207 4.6 (3.9 to 6.0); 2nd-line Cohort: CRS-207 4.0 (3.4 to 6.7); 2nd-line Cohort: Chemotherapy 6.9 (4.2 to 12.3)
• Number of Participants With Adverse Events in Each Treatment Arm Treatment Regimen (Secondary), Count of participants, Participants: Pooled Cohort: Cy/GVAX + CRS-207 44; Pooled Cohort: CRS-207 32; Pooled Cohort: Chemotherapy 15

Adverse events

Time frame: From the start of the first study drug administration on Day 1, Week 1, through 28 days after the last study drug dose, assessed up to 32 months from the date of randomization.

Serious adverse events by term

19 more terms not shown.

Other adverse events by term

17 more terms not shown.

Limitations and caveats: A high number of patients in the chemotherapy arm withdrew from the study before receiving treatment. This high dropout rate may have an impact on interpretation of the study results.

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