Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Cavity Cancer
Conditions
Keywords
fallopian tube cancer, stage II ovarian epithelial cancer, stage III ovarian epithelial cancer, stage IV ovarian epithelial cancer, peritoneal cavity cancer
Brief summary
This was a Phase 2, single-center, open-label study of recombinant vaccinia-NY-ESO-1 (rV-NY-ESO-1) and recombinant fowlpox-NY-ESO-1 (rF-NY-ESO-1) injections in patients who had a complete response to standard therapy for epithelial ovarian, fallopian tube, or primary peritoneal carcinoma and whose tumors expressed NY-ESO-1 or LAGE-1 antigen. Study objectives were to evaluate maintenance of remission at 12 months, time to failure of vaccine therapy, cellular and humoral immunity and any correlation with time to failure, and safety.
Detailed description
Patients received a single intradermal injection of rV-NY-ESO-1 (3.1 × 10\^7 plaque forming units \[PFU\]) on Day 1, followed by monthly subcutaneous injections of rF-NY-ESO-1 (7.41 × 10\^7 PFU) for 6 months (Days 29, 57, 85, 113, 141, and 169) or until observation of treatment-related ≥ grade 3 toxicity or disease progression. Study injections were administered during a 28-week evaluation period. Patients returned to the clinic for follow-up on Day 197 (i.e., 28 days after the last study injection) and every 2 months thereafter for at least 12 months. In patients with measurable disease, tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Patients were monitored continuously for safety for the duration of study participation.
Interventions
BIOLOGICALrV-NY-ESO-1 vaccine
Patients received a single intradermal injection of rV-NY-ESO-1 (3.1 × 10\^7 PFU) on Day 1.
BIOLOGICALrF-NY-ESO-1 vaccine
Patients received subcutaneous injections of rF-NY-ESO-1 (7.41 × 10\^7 PFU) on Days 29, 57, 85, 113, 141, and 169.
Sponsors
Roswell Park Cancer Institute
Ludwig Institute for Cancer Research
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically documented epithelial carcinoma arising in the ovary, fallopian tube, or peritoneum, from stage II to IV at diagnosis. 2. Received initial surgery and chemotherapy with at least one platinum-based chemotherapy regimen. 3. Demonstrated complete response to first line therapy as evidenced by negative clinical examination, cancer antigen (CA)-125 tumor marker, and computed tomography (CT) scan. In addition, if second-look surgery was performed, patients must have had no evidence of microscopic or macroscopic disease. Patients must have been within 6 months of completing their first line platinum-based chemotherapy. These patients would normally enter a period of observation as standard management. 4. Tumor expression of 1) NY-ESO-1 by reverse transcription-polymerase chain reaction (RT-PCR) analysis, preferably, or immunohistochemistry; or 2) LAGE-1 by RT-PCR. 5. Expected survival of at least 6 months. 6. Full recovery from surgery. 7. Karnofsky performance status of 70% or more. 8. Patients must have had the following clinical laboratory results: * neutrophil count: ≥ 1.5 x 10\^9/L * lymphocyte count: ≥ 0.5 x 10\^9/L * platelet count: ≥ 100 x 10\^9/L * serum creatinine: ≤ 2 mg/dL * serum bilirubin: ≤ 2 mg/dL 9. Ability to avoid close contact with children \< 3 years of age; pregnant or breast feeding women; individuals with active, or a history of, eczema or atopic dermatitis or other skin disorders such as burns, chickenpox, shingles, impetigo, herpes, severe acne, or psoriasis; and immunocompromised individuals (human immunodeficiency virus \[HIV\], leukemia, lymphoma, solid organ transplantation, generalized malignancy, cellular or humoral immunodeficiency syndromes, patients currently receiving cytotoxic chemotherapies, radiation, or high dose corticosteroids). 10. Have been informed of other treatment options. 11. Age ≥ 18 years. 12. Able and willing to give valid written informed consent.
Exclusion criteria
1. Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may have been available. 2. Other serious illnesses (eg, serious infections requiring antibiotics, bleeding disorders). 3. History of current eczema or atopic dermatitis. 4. History of autoimmune disease (eg., thyroiditis, lupus). 5. Other acute, chronic, or exfoliative skin conditions such as burns, chickenpox, shingles, impetigo, herpes, severe acne, or psoriasis. 6. Concomitant systemic treatment with corticosteroids, anti-histamine or non-steroidal anti-inflammatory drugs. Specific cyclooxygenase-2 inhibitors were permitted. 7. Chemotherapy, radiation therapy, or immunotherapy within 4 weeks before study entry (6 weeks for nitrosoureas). 8. Known HIV positivity. 9. Known allergy or severe reaction to a smallpox (vaccinia) vaccination. 10. Known allergy to eggs, determined by history. 11. Myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, chest pain or shortness of breath with activity, or other heart conditions being treated by a doctor. 12. Presence of 3 or more of the following risk factors: * Hypertension * Hypercholesterolemia * Diabetes * A first degree relative (for example, mother, father, brother, sister) who had a heart condition before the age of 50 * Current cigarette smoker 13. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment. 14. Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study. 15. Lack of availability of a patient for immunological and clinical follow-up assessment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients in Remission at 1 Year | 12 months | Time to failure (TTF) was evaluated as the crude proportion of patients in remission at 1 year, calculated as: 100 x (number of patients in remission at 1 year)/(number of patients with known status at 1 year). The Kaplan-Meier cumulative estimate of the proportion of patients in remission at 1 year was also calculated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Best Overall Tumor Response | Up to 20 months | Tumor responses were evaluated using computed tomography and were categorized according to RECIST (version 1.0) at Screening, on Days 85 and 197 and every 2 months thereafter for at least 12 months. Per RECIST, target lesions are categorized as follows: Complete Response (CR): Disappearance of all target lesions (no evaluable 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. |
| Mean Absolute Cancer Antigen-125 Values Over Time on Study | Up to 20 months | Blood samples were collected to measure serum levels of tumor marker cancer antigen (CA)-125 at Screening and on Days 1, 29, 57, 85, 113, 141, 169, and 197 and every 2 months for at least 12 months following Day 197. |
| Number of Patients With NY-ESO-1 and LAGE-1-specific Immunity | Up to 20 months | Specific antibody response to the NY-ESO-1 and LAGE-1 antigen was measured by enzyme-linked immunosorbent assay (ELISA) at Screening, Days 29, 57, 85, 113, 141, 169, 197, Month 6, and Month 12. |
| Mean Time to Failure Among Patients Who Progressed On Study | Up to 20 months | TTF was calculated as the number of days from the first dose until the patient discontinued due to progressive disease. Patients who completed the study or discontinued for other reasons were considered censored at the day of their last study visit, including the follow-up visits after Day 197. Progression was defined using the Response Evaluation Criteria In Solid Tumors (RECIST \[version 1.0\]) as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions |
| Number of Patients With Detectable T-cell Responses Following Vaccination | Up to 20 months | NY-ESO-1-specific CD8+ T cells (human leukocyte antigen \[HLA\]-A2 patients only) and NY-ESO-1-specific CD4+ T cells (HLA-DP4 patients only) were measured by interferon-gamma enzyme-linked immunosorbent spot (ELISPOT) assay. The response to the ELISPOT assay was considered to be positive if the number of spots in the peptide-exposed well was 2-fold or more higher than the number of spots in the unstimulated well, and if there was a minimum of 10 (after subtraction of background spots) peptide-specific spots/25,000 T-cells, or less if T-cell clones were used. |
| Number of Patients With Delayed-Type Hypersensitivity Reactions Following Vaccination | Up to 6 months | NY-ESO-1 antigen-specific delayed-type hypersensitivity (DTH) was measured by skin test at Screening and on Days 113 and 197. All patients were tested for the NY-ESO-1 protein, with additional DTH testing as follows: patients who were HLA-A2+ had NY-ESO-1b testing, patients who were HLA-DP4+ had NY-ESO-DP4 testing, and patients who were both HLA-A2+ and HLA-DP4+ had NY-ESO-1b and NY-ESO-DP4 testing. |
| Number of Patients With Treatment-emergent Adverse Events | Continuously for up to 20 months | Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Toxicity Criteria (CTC), version 3.0. Treatment-emergent adverse events (TEAEs) were reported based on clinical laboratory tests, physical examinations, and vital signs from pre-treatment through the study period. |
| Number of Patients With Release of Interferon-Gamma by T Cells in Response to Cancer Antigens | Up to 20 months | Intracellular cytokine staining assays were performed at Screening, Days 85 and 197, Month 6, and Month 12 to evaluate the release of interferon-gamma by CD4 and CD8 T cells following study injections. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| rV- and rF-NY-ESO-1 Patients received a single intradermal injection of rV-NY-ESO-1 (3.1 × 10\^7 PFU) on Day 1, followed by subcutaneous injections of rF-NY-ESO-1 (7.41 × 10\^7 PFU) on Days 29, 57, 85, 113, 141, and 169 or until observation of treatment-related ≥ grade 3 toxicity or disease progression. | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
| Overall Study | Progressive disease | 18 |
Baseline characteristics
| Characteristic | rV- and rF-NY-ESO-1 |
|---|---|
| Age, Continuous | 55 years |
| Body mass index | 29.5 kg/m^2 STANDARD_DEVIATION 4.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Karnofsky Performance Status 100 | 16 Participants |
| Karnofsky Performance Status 70 | 1 Participants |
| Karnofsky Performance Status 80 | 3 Participants |
| Karnofsky Performance Status 90 | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Region of Enrollment United States | 23 participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 23 |
| other Total, other adverse events | 23 / 23 |
| serious Total, serious adverse events | 4 / 23 |
Outcome results
Primary
Percentage of Patients in Remission at 1 Year
Time to failure (TTF) was evaluated as the crude proportion of patients in remission at 1 year, calculated as: 100 x (number of patients in remission at 1 year)/(number of patients with known status at 1 year). The Kaplan-Meier cumulative estimate of the proportion of patients in remission at 1 year was also calculated.
Time frame: 12 months
Population: The Full Analysis Set includes all patients who received at least 1 injection with rV-NY-ESO-1 or rF-NY-ESO-1 and met the entry criterion of having epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. One patient with breast cancer was treated in the protocol under compassionate use and is excluded from the Full Analysis Set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| rV- and rF-NY-ESO-1 | Percentage of Patients in Remission at 1 Year | Crude rate | 38.1 percentage of participants |
| rV- and rF-NY-ESO-1 | Percentage of Patients in Remission at 1 Year | Kaplan-Meier cumulative rate | 38.8 percentage of participants |
Secondary
Mean Absolute Cancer Antigen-125 Values Over Time on Study
Blood samples were collected to measure serum levels of tumor marker cancer antigen (CA)-125 at Screening and on Days 1, 29, 57, 85, 113, 141, 169, and 197 and every 2 months for at least 12 months following Day 197.
Time frame: Up to 20 months
Population: The Full Analysis Set includes all patients who received at least 1 injection with rV-NY-ESO-1 or rF-NY-ESO-1 and met the entry criterion of having epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. One patient with breast cancer was treated in the protocol under compassionate use and is excluded from the Full Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rV- and rF-NY-ESO-1 | Mean Absolute Cancer Antigen-125 Values Over Time on Study | CA-125 at Baseline | 17.9 U/mL | Standard Deviation 15.4 |
| rV- and rF-NY-ESO-1 | Mean Absolute Cancer Antigen-125 Values Over Time on Study | CA-125 at Day 29 | 27.5 U/mL | Standard Deviation 40.7 |
| rV- and rF-NY-ESO-1 | Mean Absolute Cancer Antigen-125 Values Over Time on Study | CA-125 at Day 57 | 74.8 U/mL | Standard Deviation 203.7 |
| rV- and rF-NY-ESO-1 | Mean Absolute Cancer Antigen-125 Values Over Time on Study | CA-125 at Day 85 | 12.8 U/mL | Standard Deviation 9.6 |
| rV- and rF-NY-ESO-1 | Mean Absolute Cancer Antigen-125 Values Over Time on Study | CA-125 at Day 113 | 20.4 U/mL | Standard Deviation 33.6 |
| rV- and rF-NY-ESO-1 | Mean Absolute Cancer Antigen-125 Values Over Time on Study | CA-125 at Day 141 | 11.8 U/mL | Standard Deviation 7.2 |
| rV- and rF-NY-ESO-1 | Mean Absolute Cancer Antigen-125 Values Over Time on Study | CA-125 at Day 169 | 14.1 U/mL | Standard Deviation 9.3 |
| rV- and rF-NY-ESO-1 | Mean Absolute Cancer Antigen-125 Values Over Time on Study | CA-125 at Day 197 | 16.0 U/mL | Standard Deviation 13.4 |
| rV- and rF-NY-ESO-1 | Mean Absolute Cancer Antigen-125 Values Over Time on Study | Follow-up at Month 2 | 80.7 U/mL | Standard Deviation 205.9 |
| rV- and rF-NY-ESO-1 | Mean Absolute Cancer Antigen-125 Values Over Time on Study | Follow-up at Month 4 | 16.0 U/mL | Standard Deviation 14.6 |
| rV- and rF-NY-ESO-1 | Mean Absolute Cancer Antigen-125 Values Over Time on Study | Follow-up at Month 6 | 80.4 U/mL | Standard Deviation 187.2 |
| rV- and rF-NY-ESO-1 | Mean Absolute Cancer Antigen-125 Values Over Time on Study | Follow-up at Month 8 | 10.6 U/mL | Standard Deviation 3.5 |
| rV- and rF-NY-ESO-1 | Mean Absolute Cancer Antigen-125 Values Over Time on Study | Follow-up at Month 10 | 59.5 U/mL | Standard Deviation 120.5 |
| rV- and rF-NY-ESO-1 | Mean Absolute Cancer Antigen-125 Values Over Time on Study | Follow-up at Month 12 | 16.8 U/mL | Standard Deviation 12.6 |
Secondary
Mean Time to Failure Among Patients Who Progressed On Study
TTF was calculated as the number of days from the first dose until the patient discontinued due to progressive disease. Patients who completed the study or discontinued for other reasons were considered censored at the day of their last study visit, including the follow-up visits after Day 197. Progression was defined using the Response Evaluation Criteria In Solid Tumors (RECIST \[version 1.0\]) as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: Up to 20 months
Population: The Full Analysis Set includes all patients who received at least 1 injection with rV-NY-ESO-1 or rF-NY-ESO-1 and met the entry criterion of having epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. TTF was calculated for the subset of patients who had disease progression at any time.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rV- and rF-NY-ESO-1 | Mean Time to Failure Among Patients Who Progressed On Study | 253.1 days | Standard Deviation 160.4 |
Secondary
Number of Patients With Best Overall Tumor Response
Tumor responses were evaluated using computed tomography and were categorized according to RECIST (version 1.0) at Screening, on Days 85 and 197 and every 2 months thereafter for at least 12 months. Per RECIST, target lesions are categorized as follows: Complete Response (CR): Disappearance of all target lesions (no evaluable 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.
Time frame: Up to 20 months
Population: The Full Analysis Set includes all patients who received at least 1 injection with rV-NY-ESO-1 or rF-NY-ESO-1 and met the entry criterion of having epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. One patient with breast cancer was treated in the protocol under compassionate use and is excluded from the Full Analysis Set.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| rV- and rF-NY-ESO-1 | Number of Patients With Best Overall Tumor Response | Response at Day 85 | Stable Disease | 3 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Best Overall Tumor Response | Response at Day 85 | Progressive Disease | 0 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Best Overall Tumor Response | Response at Day 85 | No Evaluable Disease | 15 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Best Overall Tumor Response | Response at Day 85 | Missing/Not Done | 4 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Best Overall Tumor Response | Response at Day 197 | Stable Disease | 3 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Best Overall Tumor Response | Response at Day 197 | Progressive Disease | 1 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Best Overall Tumor Response | Response at Day 197 | No Evaluable Disease | 11 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Best Overall Tumor Response | Response at Day 197 | Missing/Not Done | 7 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Best Overall Tumor Response | Response at 12-Month Follow-up | Stable Disease | 0 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Best Overall Tumor Response | Response at 12-Month Follow-up | Progressive Disease | 0 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Best Overall Tumor Response | Response at 12-Month Follow-up | No Evaluable Disease | 4 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Best Overall Tumor Response | Response at 12-Month Follow-up | Missing/Not Done | 18 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Best Overall Tumor Response | Response at End of Study | Stable Disease | 3 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Best Overall Tumor Response | Response at End of Study | Progressive Disease | 4 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Best Overall Tumor Response | Response at End of Study | No Evaluable Disease | 0 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Best Overall Tumor Response | Response at End of Study | Missing/Not Done | 15 Participants |
Secondary
Number of Patients With Delayed-Type Hypersensitivity Reactions Following Vaccination
NY-ESO-1 antigen-specific delayed-type hypersensitivity (DTH) was measured by skin test at Screening and on Days 113 and 197. All patients were tested for the NY-ESO-1 protein, with additional DTH testing as follows: patients who were HLA-A2+ had NY-ESO-1b testing, patients who were HLA-DP4+ had NY-ESO-DP4 testing, and patients who were both HLA-A2+ and HLA-DP4+ had NY-ESO-1b and NY-ESO-DP4 testing.
Time frame: Up to 6 months
Population: The Full Analysis Set includes all patients who received at least 1 injection with rV-NY-ESO-1 or rF-NY-ESO-1 and met the entry criterion of having epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. One patient with breast cancer was treated in the protocol under compassionate use and is excluded from the Full Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rV- and rF-NY-ESO-1 | Number of Patients With Delayed-Type Hypersensitivity Reactions Following Vaccination | NY-ESO-1 protein: Induration at Screening | 1 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Delayed-Type Hypersensitivity Reactions Following Vaccination | NY-ESO-1 protein: Redness at Screening | 5 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Delayed-Type Hypersensitivity Reactions Following Vaccination | NY-ESO-1 protein: Induration at Day 113 | 1 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Delayed-Type Hypersensitivity Reactions Following Vaccination | NY-ESO-1 protein: Redness at Day 113 | 4 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Delayed-Type Hypersensitivity Reactions Following Vaccination | NY-ESO-1 protein: Induration at Day 197 | 0 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Delayed-Type Hypersensitivity Reactions Following Vaccination | NY-ESO-1 protein: Redness at Day 197 | 1 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Delayed-Type Hypersensitivity Reactions Following Vaccination | NY-ESO-1b: Induration at Screening | 1 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Delayed-Type Hypersensitivity Reactions Following Vaccination | NY-ESO-1b: Redness at Screening | 1 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Delayed-Type Hypersensitivity Reactions Following Vaccination | NY-ESO-1b: Induration at Day 113 | 0 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Delayed-Type Hypersensitivity Reactions Following Vaccination | NY-ESO-1b: Redness at Day 113 | 0 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Delayed-Type Hypersensitivity Reactions Following Vaccination | NY-ESO-1b: Induration at Day 197 | 0 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Delayed-Type Hypersensitivity Reactions Following Vaccination | NY-ESO-1b: Redness at Day 197 | 0 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Delayed-Type Hypersensitivity Reactions Following Vaccination | NY-ESO-DP4: Induration at Screening | 0 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Delayed-Type Hypersensitivity Reactions Following Vaccination | NY-ESO-DP4: Redness at Screening | 2 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Delayed-Type Hypersensitivity Reactions Following Vaccination | NY-ESO-DP4: Induration at Day 113 | 0 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Delayed-Type Hypersensitivity Reactions Following Vaccination | NY-ESO-DP4: Redness at Day 113 | 0 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Delayed-Type Hypersensitivity Reactions Following Vaccination | NY-ESO-DP4: Induration at Day 197 | 0 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Delayed-Type Hypersensitivity Reactions Following Vaccination | NY-ESO-DP4: Redness at Day 197 | 0 Participants |
Secondary
Number of Patients With Detectable T-cell Responses Following Vaccination
NY-ESO-1-specific CD8+ T cells (human leukocyte antigen \[HLA\]-A2 patients only) and NY-ESO-1-specific CD4+ T cells (HLA-DP4 patients only) were measured by interferon-gamma enzyme-linked immunosorbent spot (ELISPOT) assay. The response to the ELISPOT assay was considered to be positive if the number of spots in the peptide-exposed well was 2-fold or more higher than the number of spots in the unstimulated well, and if there was a minimum of 10 (after subtraction of background spots) peptide-specific spots/25,000 T-cells, or less if T-cell clones were used.
Time frame: Up to 20 months
Population: The Full Analysis Set includes all patients who received at least 1 injection with rV-NY-ESO-1 or rF-NY-ESO-1 and met the entry criterion of having epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. One patient with breast cancer was treated in the protocol under compassionate use and is excluded from the Full Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rV- and rF-NY-ESO-1 | Number of Patients With Detectable T-cell Responses Following Vaccination | Detectable CD4+ T-cell response | 20 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Detectable T-cell Responses Following Vaccination | Detectable CD8+ T-cell response | 10 Participants |
Secondary
Number of Patients With NY-ESO-1 and LAGE-1-specific Immunity
Specific antibody response to the NY-ESO-1 and LAGE-1 antigen was measured by enzyme-linked immunosorbent assay (ELISA) at Screening, Days 29, 57, 85, 113, 141, 169, 197, Month 6, and Month 12.
Time frame: Up to 20 months
Population: The Full Analysis Set includes all patients who received at least 1 injection with rV-NY-ESO-1 or rF-NY-ESO-1 and met the entry criterion of having epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. One patient with breast cancer was treated in the protocol under compassionate use and is excluded from the Full Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rV- and rF-NY-ESO-1 | Number of Patients With NY-ESO-1 and LAGE-1-specific Immunity | Screening: NY-ESO-1 Positive | 3 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With NY-ESO-1 and LAGE-1-specific Immunity | Screening: LAGE-1 Positive | 2 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With NY-ESO-1 and LAGE-1-specific Immunity | Day 29: NY-ESO-1 Positive | 7 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With NY-ESO-1 and LAGE-1-specific Immunity | Day 29: LAGE-1 Positive | 5 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With NY-ESO-1 and LAGE-1-specific Immunity | Day 57: NY-ESO-1 Positive | 6 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With NY-ESO-1 and LAGE-1-specific Immunity | Day 57: LAGE-1 Positive | 4 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With NY-ESO-1 and LAGE-1-specific Immunity | Day 85: NY-ESO-1 Positive | 5 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With NY-ESO-1 and LAGE-1-specific Immunity | Day 85: LAGE-1 Positive | 4 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With NY-ESO-1 and LAGE-1-specific Immunity | Day 113: NY-ESO-1 Positive | 6 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With NY-ESO-1 and LAGE-1-specific Immunity | Day 113: LAGE-1 Positive | 3 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With NY-ESO-1 and LAGE-1-specific Immunity | Day 141: NY-ESO-1 Positive | 5 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With NY-ESO-1 and LAGE-1-specific Immunity | Day 141: LAGE-1 Positive | 3 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With NY-ESO-1 and LAGE-1-specific Immunity | Day 169: NY-ESO-1 Positive | 5 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With NY-ESO-1 and LAGE-1-specific Immunity | Day 169: LAGE-1 Positive | 3 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With NY-ESO-1 and LAGE-1-specific Immunity | Day 197: NY-ESO-1 Positive | 5 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With NY-ESO-1 and LAGE-1-specific Immunity | Day 197: LAGE-1 Positive | 3 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With NY-ESO-1 and LAGE-1-specific Immunity | Month 6: NY-ESO-1 Positive | 4 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With NY-ESO-1 and LAGE-1-specific Immunity | Month 6: LAGE-1 Positive | 0 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With NY-ESO-1 and LAGE-1-specific Immunity | Month 12: NY-ESO-1 Positive | 1 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With NY-ESO-1 and LAGE-1-specific Immunity | Month 12: LAGE-1 Positive | 1 Participants |
Secondary
Number of Patients With Release of Interferon-Gamma by T Cells in Response to Cancer Antigens
Intracellular cytokine staining assays were performed at Screening, Days 85 and 197, Month 6, and Month 12 to evaluate the release of interferon-gamma by CD4 and CD8 T cells following study injections.
Time frame: Up to 20 months
Population: The Full Analysis Set includes all patients who received at least 1 injection with rV-NY-ESO-1 or rF-NY-ESO-1 and met the entry criterion of having epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. One patient with breast cancer was treated in the protocol under compassionate use and is excluded from the Full Analysis Set.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| rV- and rF-NY-ESO-1 | Number of Patients With Release of Interferon-Gamma by T Cells in Response to Cancer Antigens | Screening: CD4 | Positive | 10 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Release of Interferon-Gamma by T Cells in Response to Cancer Antigens | Screening: CD4 | Negative | 12 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Release of Interferon-Gamma by T Cells in Response to Cancer Antigens | Screening: CD8 | Positive | 2 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Release of Interferon-Gamma by T Cells in Response to Cancer Antigens | Screening: CD8 | Negative | 20 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Release of Interferon-Gamma by T Cells in Response to Cancer Antigens | Day 85: CD4 | Positive | 13 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Release of Interferon-Gamma by T Cells in Response to Cancer Antigens | Day 85: CD4 | Negative | 5 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Release of Interferon-Gamma by T Cells in Response to Cancer Antigens | Day 85: CD8 | Positive | 6 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Release of Interferon-Gamma by T Cells in Response to Cancer Antigens | Day 85: CD8 | Negative | 12 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Release of Interferon-Gamma by T Cells in Response to Cancer Antigens | Day 197: CD4 | Positive | 12 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Release of Interferon-Gamma by T Cells in Response to Cancer Antigens | Day 197: CD4 | Negative | 3 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Release of Interferon-Gamma by T Cells in Response to Cancer Antigens | Day 197: CD8 | Positive | 5 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Release of Interferon-Gamma by T Cells in Response to Cancer Antigens | Day 197: CD8 | Negative | 9 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Release of Interferon-Gamma by T Cells in Response to Cancer Antigens | Month 6: CD4 | Positive | 6 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Release of Interferon-Gamma by T Cells in Response to Cancer Antigens | Month 6: CD4 | Negative | 2 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Release of Interferon-Gamma by T Cells in Response to Cancer Antigens | Month 6: CD8 | Positive | 3 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Release of Interferon-Gamma by T Cells in Response to Cancer Antigens | Month 6: CD8 | Negative | 5 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Release of Interferon-Gamma by T Cells in Response to Cancer Antigens | Month 12: CD4 | Positive | 3 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Release of Interferon-Gamma by T Cells in Response to Cancer Antigens | Month 12: CD4 | Negative | 1 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Release of Interferon-Gamma by T Cells in Response to Cancer Antigens | Month 12: CD8 | Positive | 1 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Release of Interferon-Gamma by T Cells in Response to Cancer Antigens | Month 12: CD8 | Negative | 3 Participants |
Secondary
Number of Patients With Treatment-emergent Adverse Events
Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Toxicity Criteria (CTC), version 3.0. Treatment-emergent adverse events (TEAEs) were reported based on clinical laboratory tests, physical examinations, and vital signs from pre-treatment through the study period.
Time frame: Continuously for up to 20 months
Population: The Safety Analysis Set includes all patients who received at least 1 injection with rV-NY-ESO-1 or rF-NY-ESO-1.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rV- and rF-NY-ESO-1 | Number of Patients With Treatment-emergent Adverse Events | Maximum grade 3 TEAE | 3 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Treatment-emergent Adverse Events | Any TEAE | 23 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Treatment-emergent Adverse Events | Maximum grade 1 TEAE | 3 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Treatment-emergent Adverse Events | Maximum grade 2 TEAE | 15 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Treatment-emergent Adverse Events | Maximum grade 4 TEAE | 2 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Treatment-emergent Adverse Events | Treatment-related TEAE | 9 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Treatment-emergent Adverse Events | Serious TEAE | 4 Participants |
| rV- and rF-NY-ESO-1 | Number of Patients With Treatment-emergent Adverse Events | TEAE Leading to Treatment Discontinuation | 2 Participants |