Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Skin and Connective Tissue Diseases

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Prostatic Neoplasms

Breast Neoplasms

Esophageal Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Melanoma

Gastrointestinal Stromal Tumors

Head and Neck Neoplasms

Carcinoma, Transitional Cell

Sarcoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Connective and Soft Tissue

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Neoplasms, Connective Tissue

Esophageal Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Transitional Cell Carcinoma

Soft Tissue Sarcoma

All Drugs and Chemicals

Vaccines

Subjects received MBV at a starting dose of 250 EU (dose level 1) twice weekly, with intrasubject dose escalations for each subsequent administration in the absence of a DLT until the desired pyrogenic effect was observed. The maximum possible dose to be investigated was 547,000 EU (dose level 8).

Subjects received MBV twice weekly at the fixed dose (60,800 EU \[dose level 6\]) that was determined to be the pyrogenic dose level in Cohort 1.

MBV was administered twice weekly by subcutaneous injection in Cohort 1 and by intralesional (preferred) or subcutaneous (if intralesional not possible) injection in Cohort 2. In Cohort 1, the MBV starting dose was 250 EU (dose level 1) with possible intrasubject escalations up to 547,000 EU (dose level 8). In Cohort 2, all subjects received MBV at a fixed dose of 60,800 EU (dose level 6).

Mixed bacterial vaccine

Elke Jager, MD

This was a phase 1, open-label, multiple dose, single-arm study. The mixed bacteria vaccine (MBV) was administered at a starting dose of 250 EU (1 µL) and escalated in each subject to a dose inducing the desired pyrogenic effect, defined as a body temperature of 38°C to 39.5°C. The primary objective was to determine the safety profile of MBV in subjects with malignant tumors that expressed the NY-ESO-1 antigen and to identify the dose that induced the desired pyrogenic effect. Secondary objectives were to evaluate the immunological effects and tumor response of subjects following vaccination.

Subjects in Cohort 1 were enrolled to receive MBV subcutaneously at a starting dose of 250 EU (1 µL; dose level 1) administered twice weekly. In the absence of a dose-limiting toxicity (DLT), the MBV dose was escalated in each subject to the MBV dose that elicited the desired pyrogenic effect, or up to the maximum dose of 547,000 EU (dose level 8). Once the desired pyrogenic effect was observed, subjects received MBV twice weekly for 4 doses at the pyrogenic dose level.

Subjects in Cohort 2 were enrolled to receive MBV at the pyrogenic dose level (determined to be 60,800 EU \[dose level 6\]) twice weekly for 6 weeks. Vaccinations were injected intralesionally if possible and subcutaneously if intralesional injection was not possible. If a fever of 39.5°C to 40°C was observed, the subject's dose was reduced to dose level 5 (20,300 EU \[81 μL\]).

Subjects were observed at the clinic for up to 6 hours following each vaccination, with vital signs measured hourly. At baseline and throughout the study, subjects were assessed for NY-ESO-1-specific humoral and cellular immunity, chemistry, hematology, and cytokine analysis (interleukin \[IL\]-1, IL-6, interferon \[IFN\]-γ, and tumor necrosis factor \[TNF\]-α). Safety was monitored continuously throughout the study.

A Phase 1 Study of Mixed Bacteria Vaccine (MBV) in Patients With Tumors Expressing NY-ESO-1 Antigen

A Phase 1 Study of Mixed Bacteria Vaccine (MBV) in Patients With Tumors Expressing NY-ESO-1 Antigen.

Analysis of treatment-emergent adverse events (TEAEs) reported from clinical laboratory tests, physical examinations, and vital signs from pre-treatment through 4 weeks after the last dose of study treatment.

Intrasubject dose escalation performed over a dose range of 250 to 547,000 EU until achievement of the desired pyrogenic effects (i.e., body temperature increase to 38°C to 39.5°C). Of note, the median pyrogenic dose was 60,800 EU.

Serum NY-ESO-1-specific immune responses evaluated by humoral immunity (antibodies measured by ELISA), cellular immunity (CD8+ T-cell and CD4+ T-cell measured by ELISPOT), and cytokine activation (measured by ELISA) from pre-treatment through 4 weeks after the last dose of study treatment. \[Note: CD = cluster of differentiation; IFN =interferon; IL = interleukin; TNF = tumor necrosis factor\]

Tumor responses evaluated using computed tomography and categorized according to RECIST version 1.0 at pre-treatment and 4 weeks after the last dose of study treatment. Per RECIST v1.0 for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions \[no evidence of disease\]; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.

Krankenhaus Nordwest

Ludwig Institute for Cancer Research

AE documentation included onset/resolution dates, severity using NCI CTCAE (v3.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.

Subjects received MBV twice weekly by subcutaneous injection at a starting dose of 250 EU (dose level 1), with intrasubject dose escalations for each subsequent administration in the absence of a DLT until the desired pyrogenic effect was observed.

Cohort 1

Subjects received MBV twice weekly by intralesional (preferred) or subcutaneous (if intralesional not possible) injection at the fixed dose (60,800 EU \[dose level 6\]) that was determined to be the pyrogenic dose level in Cohort 1.

Cohort 2

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Germany

Region of Enrollment

Prostate cancer

Head and neck cancer

Breast cancer

Transitional cell carcinoma

Diagnosis at Study Entry

Stage IV Disease at Study Entry

100%

100%: Normal no complaints; no evidence of disease. 90%: Able to carry on normal activity; minor signs or symptoms of disease. 80%: Normal activity with effort; some signs or symptoms of disease. 70%: Cares for self; unable to carry on normal activity or to do active work.

Baseline Karnofsky Performance Status

Jonathan Skipper PhD

Any TEAE

Grade 3 TEAE

Grade 4 TEAE

Grade 5 TEAE (Death)

Treatment-related TEAE

TEAE leading to withdrawal

Cohort 1 (Safety Analysis Set)

Cohort 2 (Safety Analysis Set)

The Safety Analysis Set comprises all subjects who received at least 1 dose of study drug.

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

Pyrogenic Dose: 250 EU

Pyrogenic Dose: 750 EU

Pyrogenic Dose: 2250 EU

Pyrogenic Dose: 20,300 EU

Pyrogenic Dose: 60,800 EU

Pyrogenic Dose: 182,000 EU

Pyrogenic Dose: 547,000 EU

Desired Pyrogenic Effect Not Observed

Discontinued Before Pyrogenic Effect Observed

Number of Participants With Pyrogenicity at Each Dose Level Tested in the Intrasubject Dose Escalation Performed Over a Dose Range of 250 to 547,000 EU

Antibody Sero(+) Pre- and Post-treatment

Antibody Sero(-) Pre- and Post-treatment

Antibody Sero(-) Pre-treatment, (+) Post-treatment

CD4+ Pre- and Post-treatment

CD4- Pre- and Post-treatment

CD4 Not Evaluable

CD8+ Pre- and Post-treatment

CD8- Pre- and Post-treatment

Increase of ≥ 2 Cytokines Post-treatment

IL-6 Increase Post-treatment

TNF-α Increase Post-treatment

IFN-γ Increase Post-treatment

IL-2 Increase Post-treatment

IL-Iβ Increase Post-treatment

IL-8 Increase Post-treatment

IL-10 Increase Post-treatment

IL-12 Increase Post-treatment

IL-5 Increase Post-treatment

Cohort 1 (Immune Response Analysis Set)

The Immune Response Analysis Set comprises all subjects who achieved the desired pyrogenic effects.

Number of Participants With Serum NY-ESO-1-specific Immune Responses

No evidence of disease

Partial response

Stable disease

Progressive disease

Cohort 1 (Tumor Response Analysis Set)

Cohort 2 (Tumor Response Analysis Set)

The Tumor Response Analysis Set comprises all subjects who had an end-of-study tumor assessment performed.

Number of Participants With Best Overall Tumor Response

Subjects received MBV twice weekly by subcutaneous injection at a starting dose of 250 EU (dose level 1), with intrasubject dose escalations for each subsequent administration in the absence of a dose-limiting toxicity (DLT) until the desired pyrogenic effect was observed.

Overall Study

Spots Global Cancer Trial Database for mixed bacterial vaccine