Phase 1 Study of NY-ESO-1 Overlapping Peptides in Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Phase 1

Completed

• Conditions: Fallopian Tube Cancer; Primary Peritoneal Cancer; Epithelial Ovarian Cancer
• Interventions: Biological: NY-ESO-1 OLP4 + Montanide; Biological: NY-ESO-1 OLP4; Biological: NY-ESO-1 OLP4 + Montanide + Poly-ICLC

• Registration Number: NCT00616941
• Lead Sponsor: Ludwig Institute for Cancer Research

Brief Summary

This was a Phase 1, open-label study of repeated vaccination with NY-ESO-1 overlapping peptides (OLP4) with or without the immunoadjuvants Montanide and polyinosinic-polycytidylic acid - poly-L-lysine carboxymethylcellulose (poly-ICLC) administered every 3 weeks for a total of 5 vaccinations in subjects with epithelial ovarian, fallopian tube, or primary peritoneal cancer in second or third clinical remission. Study objectives included determination of the safety and immunogenicity following vaccination.

Detailed Description

Subjects received NY-ESO-1 OLP4 by subcutaneous injection once every 3 weeks (Weeks 1, 4, 7, 10, and 13) for a total of 5 vaccinations.

Subjects were assigned sequentially to 1 of 3 dosing cohorts:

Cohort 1: received NY-ESO-1 OLP4 alone; Cohort 2: received NY-ESO-1 OLP4 in combination with Montanide; Cohort 3: received NY-ESO-1 OLP4 in combination with Montanide and Poly-ICLC.

Enrollment into each subsequent dosing cohort was dependent on a dose-limiting toxicity (DLT) rate of \<33% in the preceding cohort. No dose escalation was planned.

Subjects were observed by study staff for up to 30 minutes following each vaccination. Immunologic assessments were performed prior to the first vaccination and 3 weeks after each vaccination. Toxicity assessments were performed with each vaccination and 3 weeks after the completion of therapy (ie, the final study visit was Week 16). Immunologic assessments included measurement of the anti-NY-ESO-1 antibody by enzyme-linked immunsorbent assay (ELISA), detection of CD-4 and CD-8 cellular responses by tetramer and enzyme-linked immunosorbent spot assay (ELISPOT), and delayed-type hypersensitivity (DTH).

Study Timeline

• Study First Submitted: 2008-02-04
• Study First Submitted QC: 2008-02-14
• Study First Posted: 2008-02-15
• Study Start: 2008-03
• Primary Completion: 2011-06
• Study Completion: 2011-06
• Results First Submitted: 2017-04-28
• Results First Submitted QC: 2017-10-19
• Results First Posted: 2018-07-27
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-03
• Last Update Posted: 2022-10-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 28

Inclusion Criteria

1. Histologically documented epithelial carcinoma arising in the ovary, fallopian tube, or peritoneum, stage II to IV at diagnosis, and post-initial cytoreductive surgery and chemotherapy with at least one platinum-based chemotherapy regimen.

2. In second or third stable complete clinical remission, defined as a) stable cancer antigen (CA)-125 < 35 U/ml (defined as CA-125 that had not doubled from the post chemotherapy nadir), b) unremarkable physical examination, and c) no definite evidence of disease by computed tomography (CT) of the abdomen and pelvis. Lymph nodes and/or soft tissue abnormalities ≤ 1.0 cm that are often present in the pelvis were not considered definite evidence of disease.

3. Expected survival of at least 4 months.

4. Karnofsky performance scale ≥ 70%.

5. Laboratory values within the following limits:

   • Hemoglobin ≥ 10.0 g/dL
   • Neutrophil count ≥ 1.5 x 10^9/L
   • Platelet count ≥ 80 x 10^9/L
   • Serum creatinine ≤ 2.0 mg/dL
   • Serum bilirubin ≤ 2.5 x institutional upper limit of normal (ULN)
   • aspartate aminotransferase/alanine aminotransferase ≤ 2.5 x institutional ULN

6. Age ≥ 18 years.

7. ≥ 4 weeks since completion of prior cytotoxic chemotherapy.

8. Able and willing to give valid written informed consent

Exclusion Criteria

1. Clinically significant heart disease (New York Heart Association Class III or IV).
2. Serious intercurrent illness, eg, serious infections requiring prolonged parenteral antibiotics or bleeding disorders requiring hospitalization.
3. Positive stool guaiac excluding hemorrhoids.
4. Known autoimmune disease (ie, rheumatoid arthritis, ulcerative colitis, etc); or immune deficiency (human immunodeficiency virus, hypogammaglobulinemia); or known active infections with Hepatitis B or Hepatitis C; or receipt of immunosuppressive drugs such as systemic corticosteroids or cyclosporin, etc.
5. Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ.
6. History of previous severe allergic reactions to vaccines or unknown allergens.
7. Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study.
8. Lack of availability for immunological and clinical follow-up assessments.
9. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dose of study agent.
10. Pregnancy or breast-feeding.
11. Women of childbearing potential: Refusal or inability to use effective means of contraception.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 2	NY-ESO-1 OLP4 + Montanide	Subjects received 4 synthetic peptides coded by the NY-ESO-1 gene (ie, NY-ESO-1 OLP4) in combination with Montanide ISA-51 vegetable grade (VG) once every 3 weeks for a total of 5 vaccinations.
Cohort 1	NY-ESO-1 OLP4	Subjects received 4 synthetic peptides coded by the NY-ESO-1 gene (ie, NY-ESO-1 OLP4) once every 3 weeks for a total of 5 vaccinations.
Cohort 3	NY-ESO-1 OLP4 + Montanide + Poly-ICLC	Subjects received 4 synthetic peptides coded by the NY-ESO-1 gene (ie, NY-ESO-1 OLP4) in combination with Montanide ISA-51 VG and poly-ICLC once every 3 weeks for a total of 5 vaccinations.

Primary Outcome Measures

Name	Time	Method
Overview of Treatment-emergent Adverse Events (TEAEs)	Continuously for up to 16 weeks	Analysis of TEAEs reported from clinical laboratory tests, physical examinations, and vital signs from pre-treatment through 3 weeks after the last dose of study treatment.

Secondary Outcome Measures

Name	Time	Method
Cancer Antigen (CA)-125 Levels Up to 16 Weeks Post-Baseline	Screening, Week 7, and Week 16	Serum CA-125 was measured at Screening, Week 7, and Week 16. Stable CA-125 at baseline was \< 35 U/mL (defined as CA-125 that had not doubled from the post chemotherapy nadir).
Number of Patients With Delayed-type Hypersensitivity (DTH) Reactions (Induration and Redness) to NY-ESO-1 OLP4 at Screening and Week 16	Screening and Week 16	NY-ESO-1-specific DTH was measured by skin tests at Screening and again at Week 16. NY-ESO-1 OLP4 (40 µg in 0.1 mL D5W) was injected intradermally, with DTH reactions read 48 hours after injection.
Number of Patients With Detectable Serum Immunoglobulin G (IgG) Antibody Titers Against NY-ESO-1 Up to 16 Weeks Post-Baseline	Screening and Weeks 4, 7, 10, 13, and 16	Blood samples were drawn to measure immunologic response at Screening and Weeks 4, 7, 10, 13, and 16. Specific antibodies against NY-ESO-1 were measured by enzyme-linked immunosorbent assay (ELISA).
Tumor Measurement Results According to the Response Evaluation Criteria for Solid Tumors (RECIST) Up to 16 Weeks Post-Baseline	Screening and every 2 months up to Week 16	Radiographic imaging (computed tomography of the abdomen and pelvis) was obtained at Screening and every 2 months during the study, and at unscheduled time points if any clinical symptoms/examination findings warranted further evaluation or if serum CA-125 rose to \> 70 U/mL (confirmed by repeat value). Subjects may have had more than 1 location of disease.
Number of Patients With Detectable CD8+ and CD4+ T-cell Responses Up to 16 Weeks Post-Baseline	Screening and Weeks 4, 7, 10, 13, and 16	Blood samples were drawn to measure immunologic response at Screening and Weeks 4, 7, 10, 13, and 16. NY-ESO-1-specific CD8+ and CD4+ T-cell reactivity was measured by tetramer analysis (in human leukocyte antigen \[HLA\] 0201\* patients). Interferon gamma (IFN-γ) release by T cells was measured by the enzyme-linked immunospot (ELISPOT) assay. A subject was considered to have experienced a T-cell response if IFN-γ spots were detectable (\>50 spots) by ELISPOT of 50,000 CD8+ and CD4+ T cells following pre-sensitization with a pool of 20-mer OLP covering all of NY-ESO-1 and tested against Epstein-Barr virus-transformed B cells pulsed with 3 subpools of these peptides.

Trial Locations

Locations (1)

Memorial Sloan-Kettering Cancer Center; 🇺🇸 New York, New York, United States