Vaccine Therapy in Patients With Stage II, III, or IV Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer

• Sponsor: Ludwig Institute for Cancer Research (Other)
• Overall Status: Completed
• CT.gov ID: NCT00112957
• Collaborator: Roswell Park Cancer Institute (Other)
• Enrollment: 23
• Location: 1
• Arm: 1
• Actual Duration (Months): 53
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Fallopian Tube Cancer; Ovarian Cancer; Peritoneal Cavity Cancer	Biological: rV-NY-ESO-1 vaccine; Biological: rF-NY-ESO-1 vaccine	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Recombinant Vaccinia-NY-ESO-1 (rV-NY-ESO-1) and Recombinant Fowlpox-NY-ESO-1 (rF-NY-ESO-1) in Patients With Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma Whose Tumors Express NY-ESO-1 or LAGE-1 Antigen
• Actual Study Start Date: Dec 1, 2004
• Actual Primary Completion Date: May 1, 2009
• Actual Study Completion Date: May 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Biological: rV-NY-ESO-1 vaccine; Patients received a single intradermal injection of rV-NY-ESO-1 (3.1 × 10^7 PFU) on Day 1.; Biological: rF-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.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts 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

1. 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).

2. Have been informed of other treatment options.

3. Age ≥ 18 years.

4. 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

1. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.

2. Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study.

3. Lack of availability of a patient for immunological and clinical follow-up assessment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001

Sponsors and Collaborators

• Ludwig Institute for Cancer Research
• Roswell Park Cancer Institute

Investigators

• Principal Investigator: Kunle Odunsi, MD, PhD, Roswell Park Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ludwig Institute for Cancer Research
• ClinicalTrials.gov Identifier: NCT00112957
• Other Study ID Numbers: LUD 2002-012; RPCI-I-13303; CDR0000424461
• First Posted: Jun 3, 2005
• Last Update Posted: Mar 19, 2018
• Last Verified: Mar 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Ludwig Institute for Cancer Research: fallopian tube cancer; stage II ovarian epithelial cancer; stage III ovarian epithelial cancer; stage IV ovarian epithelial cancer; peritoneal cavity cancer
• Additional relevant MeSH terms: Fallopian Tube Neoplasms; Vaccines

Study Results

Participant Flow

Arm/Group Title	rV- and rF-NY-ESO-1
Arm/Group Description	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.
Period Title: Overall Study
STARTED	23
COMPLETED	4
NOT COMPLETED	19

Baseline Characteristics

Arm/Group Title	rV- and rF-NY-ESO-1
Arm/Group Description	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.
Overall Participants	23
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	55
Sex: Female, Male (Count of Participants)
Female	23 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	23 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	23 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	23 100%
Karnofsky Performance Status (Count of Participants)
70	1 4.3%
80	3 13%
90	3 13%
100	16 69.6%
Body mass index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29.5 (4.7)

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients in Remission at 1 Year
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	rV- and rF-NY-ESO-1
Arm/Group Description	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.
Measure Participants	22
Crude rate	38.1 165.7%
Kaplan-Meier cumulative rate	38.8 168.7%

2. Secondary Outcome

Title	Mean Time to Failure Among Patients Who Progressed On Study
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	rV- and rF-NY-ESO-1
Arm/Group Description	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.
Measure Participants	17
Mean (Standard Deviation) [days]	253.1 (160.4)

3. Secondary Outcome

Title	Number of Patients With Best Overall Tumor Response
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	rV- and rF-NY-ESO-1
Arm/Group Description	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.
Measure Participants	22
Stable Disease	3 13%
Progressive Disease	0 0%
No Evaluable Disease	15 65.2%
Missing/Not Done	4 17.4%
Stable Disease	3 13%
Progressive Disease	1 4.3%
No Evaluable Disease	11 47.8%
Missing/Not Done	7 30.4%
Stable Disease	0 0%
Progressive Disease	0 0%
No Evaluable Disease	4 17.4%
Missing/Not Done	18 78.3%
Stable Disease	3 13%
Progressive Disease	4 17.4%
No Evaluable Disease	0 0%
Missing/Not Done	15 65.2%

4. Secondary Outcome

Title	Mean Absolute Cancer Antigen-125 Values Over Time on Study
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	rV- and rF-NY-ESO-1
Arm/Group Description	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.
Measure Participants	22
CA-125 at Baseline	17.9 (15.4)
CA-125 at Day 29	27.5 (40.7)
CA-125 at Day 57	74.8 (203.7)
CA-125 at Day 85	12.8 (9.6)
CA-125 at Day 113	20.4 (33.6)
CA-125 at Day 141	11.8 (7.2)
CA-125 at Day 169	14.1 (9.3)
CA-125 at Day 197	16.0 (13.4)
Follow-up at Month 2	80.7 (205.9)
Follow-up at Month 4	16.0 (14.6)
Follow-up at Month 6	80.4 (187.2)
Follow-up at Month 8	10.6 (3.5)
Follow-up at Month 10	59.5 (120.5)
Follow-up at Month 12	16.8 (12.6)

5. Secondary Outcome

Title	Number of Patients With NY-ESO-1 and LAGE-1-specific Immunity
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	rV- and rF-NY-ESO-1
Arm/Group Description	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.
Measure Participants	22
Screening: NY-ESO-1 Positive	3 13%
Screening: LAGE-1 Positive	2 8.7%
Day 29: NY-ESO-1 Positive	7 30.4%
Day 29: LAGE-1 Positive	5 21.7%
Day 57: NY-ESO-1 Positive	6 26.1%
Day 57: LAGE-1 Positive	4 17.4%
Day 85: NY-ESO-1 Positive	5 21.7%
Day 85: LAGE-1 Positive	4 17.4%
Day 113: NY-ESO-1 Positive	6 26.1%
Day 113: LAGE-1 Positive	3 13%
Day 141: NY-ESO-1 Positive	5 21.7%
Day 141: LAGE-1 Positive	3 13%
Day 169: NY-ESO-1 Positive	5 21.7%
Day 169: LAGE-1 Positive	3 13%
Day 197: NY-ESO-1 Positive	5 21.7%
Day 197: LAGE-1 Positive	3 13%
Month 6: NY-ESO-1 Positive	4 17.4%
Month 6: LAGE-1 Positive	0 0%
Month 12: NY-ESO-1 Positive	1 4.3%
Month 12: LAGE-1 Positive	1 4.3%

6. Secondary Outcome

Title	Number of Patients With Release of Interferon-Gamma by T Cells in Response to Cancer Antigens
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	rV- and rF-NY-ESO-1
Arm/Group Description	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.
Measure Participants	22
Positive	10 43.5%
Negative	12 52.2%
Positive	2 8.7%
Negative	20 87%
Positive	13 56.5%
Negative	5 21.7%
Positive	6 26.1%
Negative	12 52.2%
Positive	12 52.2%
Negative	3 13%
Positive	5 21.7%
Negative	9 39.1%
Positive	6 26.1%
Negative	2 8.7%
Positive	3 13%
Negative	5 21.7%
Positive	3 13%
Negative	1 4.3%
Positive	1 4.3%
Negative	3 13%

7. Secondary Outcome

Title	Number of Patients With Detectable T-cell Responses Following Vaccination
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	rV- and rF-NY-ESO-1
Arm/Group Description	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.
Measure Participants	22
Detectable CD4+ T-cell response	20 87%
Detectable CD8+ T-cell response	10 43.5%

8. Secondary Outcome

Title	Number of Patients With Delayed-Type Hypersensitivity Reactions Following Vaccination
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	rV- and rF-NY-ESO-1
Arm/Group Description	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.
Measure Participants	22
NY-ESO-1 protein: Induration at Screening	1 4.3%
NY-ESO-1 protein: Redness at Screening	5 21.7%
NY-ESO-1 protein: Induration at Day 113	1 4.3%
NY-ESO-1 protein: Redness at Day 113	4 17.4%
NY-ESO-1 protein: Induration at Day 197	0 0%
NY-ESO-1 protein: Redness at Day 197	1 4.3%
NY-ESO-1b: Induration at Screening	1 4.3%
NY-ESO-1b: Redness at Screening	1 4.3%
NY-ESO-1b: Induration at Day 113	0 0%
NY-ESO-1b: Redness at Day 113	0 0%
NY-ESO-1b: Induration at Day 197	0 0%
NY-ESO-1b: Redness at Day 197	0 0%
NY-ESO-DP4: Induration at Screening	0 0%
NY-ESO-DP4: Redness at Screening	2 8.7%
NY-ESO-DP4: Induration at Day 113	0 0%
NY-ESO-DP4: Redness at Day 113	0 0%
NY-ESO-DP4: Induration at Day 197	0 0%
NY-ESO-DP4: Redness at Day 197	0 0%

9. Secondary Outcome

Title	Number of Patients With Treatment-emergent Adverse Events
Description	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

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set includes all patients who received at least 1 injection with rV-NY-ESO-1 or rF-NY-ESO-1.

Arm/Group Title	rV- and rF-NY-ESO-1
Arm/Group Description	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.
Measure Participants	23
Any TEAE	23 100%
Maximum grade 1 TEAE	3 13%
Maximum grade 2 TEAE	15 65.2%
Maximum grade 3 TEAE	3 13%
Maximum grade 4 TEAE	2 8.7%
Treatment-related TEAE	9 39.1%
Serious TEAE	4 17.4%
TEAE Leading to Treatment Discontinuation	2 8.7%

Adverse Events

Time Frame	All adverse events (AEs) occurring between the signing of informed consent and the off-study date were documented, regardless of the causal relationship to study drug. AEs occurring after the first dose of study drug were considered treatment emergent (i.e., TEAEs). The AE reporting period for this study was up to 20 months.
Adverse Event Reporting Description	AE documentation included onset/resolution dates, severity using the NCI CTC (version 3.0), 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 patient at the maximum reported grade.
Arm/Group Title	rV- and rF-NY-ESO-1
Arm/Group Description	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.
All Cause Mortality
	rV- and rF-NY-ESO-1
	Affected / at Risk (%)	# Events
Total	0/23 (0%)
Serious Adverse Events
	rV- and rF-NY-ESO-1
	Affected / at Risk (%)	# Events
Total	4/23 (17.4%)
Gastrointestinal disorders
Small intestinal obstruction	1/23 (4.3%)
Abdominal pain	1/23 (4.3%)
Infections and infestations
Urinary tract infection	1/23 (4.3%)
Pneumonia	1/23 (4.3%)
Septic shock	1/23 (4.3%)
Musculoskeletal and connective tissue disorders
Pathological fracture	1/23 (4.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm	1/23 (4.3%)
Psychiatric disorders
Mental status changes	1/23 (4.3%)
Respiratory, thoracic and mediastinal disorders
Cough	1/23 (4.3%)
Respiratory failure	1/23 (4.3%)
Other (Not Including Serious) Adverse Events
	rV- and rF-NY-ESO-1
	Affected / at Risk (%)	# Events
Total	23/23 (100%)
Gastrointestinal disorders
Abdominal pain	4/23 (17.4%)
Abdominal pain upper	4/23 (17.4%)
Nausea	4/23 (17.4%)
Vomiting	3/23 (13%)
Abdominal distension	2/23 (8.7%)
Diarrhoea	2/23 (8.7%)
General disorders
Chest pain	3/23 (13%)
Pyrexia	3/23 (13%)
Fatigue	2/23 (8.7%)
Injection site pruritus	2/23 (8.7%)
Injection site reaction	2/23 (8.7%)
Injection site scab	2/23 (8.7%)
Oedema peripheral	2/23 (8.7%)
Pain	2/23 (8.7%)
Infections and infestations
Nasopharyngitis	4/23 (17.4%)
Urinary tract infection	2/23 (8.7%)
Bronchitis	2/23 (8.7%)
Sinusitis	2/23 (8.7%)
Investigations
Skin test positive	20/23 (87%)
Blood creatinine increased	2/23 (8.7%)
Blood glucose increased	2/23 (8.7%)
Blood urea increased	2/23 (8.7%)
Metabolism and nutrition disorders
Hyperkalaemia	2/23 (8.7%)
Hyponatraemia	2/23 (8.7%)
Musculoskeletal and connective tissue disorders
Back pain	4/23 (17.4%)
Arthralgia	2/23 (8.7%)
Muscle spasms	2/23 (8.7%)
Pain in extremity	2/23 (8.7%)
Nervous system disorders
Neuropathy peripheral	3/23 (13%)
Dizziness	2/23 (8.7%)
Headache	2/23 (8.7%)
Psychiatric disorders
Insomnia	3/23 (13%)
Renal and urinary disorders
Pollakiuria	2/23 (8.7%)
Reproductive system and breast disorders
Breast tenderness	2/23 (8.7%)
Respiratory, thoracic and mediastinal disorders
Cough	4/23 (17.4%)
Dyspnoea	3/23 (13%)
Nasal congestion	3/23 (13%)
Wheezing	2/23 (8.7%)
Skin and subcutaneous tissue disorders
Rash	3/23 (13%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.