A Pilot Study of NY-ESO-1b Peptide Plus CpG 7909 and Montanide® ISA-51 in Patients With Cancer.

• Sponsor: Ludwig Institute for Cancer Research (Other)
• Overall Status: Completed
• CT.gov ID: NCT00199836
• Collaborator: (none)
• Enrollment: 14
• Location: 1
• Arm: 1
• Actual Duration (Months): 33.1
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This cancer vaccine research study involves the injection of the NY-ESO-1b peptide along with 2 other agents to help stimulate the immune system. Peptides are small fragments of protein. NY- ESO-1 peptides are normally found in the testis and the placenta. They have also been found on various types of cancer cells. The purpose is to stimulate the immune system to react against the peptides that are found on cancer cells.

Condition or Disease	Intervention/Treatment	Phase
Cancer; Neoplasm	Biological: NY-ESO-1b peptide plus CpG 7909 and Montanide® ISA-51	Phase 1

Detailed Description

This is a pilot study of patients of HLA-A2 phenotype whose tumor expresses the NY-ESO-1 or LAGE-1 antigen. Patients will receive NY-ESO-1b peptide mixed with 0.5 milliliter (mL) of Montanide® ISA-51 and 1 mg of CpG 7909 given every three weeks for four doses by subcutaneous injection. There will be a three-week follow-up period after the fourth injection making the cycle 13 weeks long. In the absence of toxicity and progressive disease, a second cycle will be offered to patients who have received four vaccinations.

The primary objective is to evaluate the immune response (antibodies, CD8+ T-cells, and DTH) and safety to vaccination with NY-ESO-1b peptide mixed with CpG 7909 and Montanide® in patients with cancer expressing NY-ESO-1 or LAGE-1. The secondary objective is to document tumor responses in patients with evaluable or measurable disease.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Study of NY-ESO-1b Peptide Plus CpG 7909 and Montanide® ISA-51 in Patients With Cancer Expressing NY-ESO-1 or LAGE-1.
• Actual Study Start Date: Sep 3, 2003
• Actual Primary Completion Date: Sep 5, 2005
• Actual Study Completion Date: Jun 6, 2006

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Patients with Cancer Expressing NY-ESO-1 or LAGE-1 Antigen. NY-ESO-1b peptide, 100 μg mixed with 1 mg CpG 7909 and 0.5mL of Montanide® ISA-51 was administered to patients with cancer expressing NY-ESO-1 or LAGE-1 antigen. The injections were given subcutaneously beginning on week 1 and repeated every three weeks for 4 injections total. There was a 3 week follow-up period after the last injection. In the absence of toxicity and progressive disease (PD), a second cycle was offered to patients who received 4 vaccinations.

Biological: NY-ESO-1b peptide plus CpG 7909 and Montanide® ISA-51

Outcome Measures

Primary Outcome Measures

1. Number of Patients With NY-ESO-1 Specific Humoral Immunity as Determined by an Increase in Antibody Titer From Baseline. [up to 27 weeks]

   Blood samples were obtained at baseline (prior to the first dose), prior to the second, third and fourth injection and 2 weeks after the fourth injection in both cycles 1 and 2 for the assessment of NY-ESO-1 specific antibodies by an enzyme-linked immunosorbent assay (ELISA). A positive response was a readable optical density at 280 nm.

2. Number of Patients With NY-ESO-1 Specific Cellular Immunity as Measured by an Increase in NY-ESO-1b Specific CD8+ T-cells Following Treatment. [up to 27 weeks]

   Blood samples were obtained at baseline, prior to the second, third and fourth injection and 2 weeks after the fourth injection in both cycles 1 and 2 for the assessment of NY-ESO-1b specific CD8+ T-cells by ELISPOT assays.

3. Number of Patients With Delayed-Type Hypersensitivity (DTH) Skin Reactions to NY-ESO-1b Peptide [up to 25 weeks]

   10 mcg NY-ESO-1b peptide was injected intradermally at a separate site from the vaccination at baseline and after the second and fourth injection of each cycle. Assessment of DTH reactions as evidenced by redness and induration was performed 48 h after injection. The number of patients with DTH positive skin reactions was reported at each timepoint.

4. Safety as Measured by the Number of Patients With Dose Limiting Toxicities (DLT) [up to 28 weeks]

   DLT was defined as the following toxicities definitely, probably, or possibly related to the administration of NY-ESO-1b peptide, 100 μg mixed with 1 mg CpG 7909 and 0.5mL of Montanide® ISA-51: ≥ Grade 2 autoimmune phenomena Asymptomatic bronchospasm or generalized urticaria ≥ Grade 3 hematological and non hematological toxicities.

Secondary Outcome Measures

1. Number of Patients With Tumor Responses as Measured by the Response Evaluation Criteria in Solid Tumors (RECIST) [up to 28 weeks]

   Computed tomography (CT) scans were performed at screening, and during weeks 13 and 28. Response was assessed using RECIST version 1.0 (Therasse et al, J Natl Cancer Inst 2000; 92:205-16). 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. No evidence of disease (NED): no target or non-target lesions at baseline and no new lesions identified on post-baseline scans.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed metastatic, measurable cancer or resected high risk Stage III/IV; resected Stage II, III, or IV non-small cell lung cancer or esophageal cancer who have declined, failed, or completed standard therapy; tumor expression of NY-ESO-1 or LAGE-1 antigen; HLA-A2 positive; Karnofsky performance status greater than or equal to 60%; hematology and biochemistry laboratory results within the limits normally expected for the patient population; age greater than or equal to 18.

Exclusion Criteria:

• Clinically significant heart disease; other serious illnesses; patients with serious intercurrent illness, requiring hospitalization; patients taking immunosuppressive drugs; autoimmune disease; known HIV positivity; other active malignancy within 1 year prior to entry into the study; participation in chemotherapy, radiation therapy, or any other clinical trial involving another investigational agent within 4 weeks prior to enrollment; pregnancy or breastfeeding; women of childbearing potential: refusal or inability to use effective means of contraception.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Krankenhaus Nordwest	Frankfurt		Germany

Sponsors and Collaborators

• Ludwig Institute for Cancer Research

Investigators

• Principal Investigator: Nasser K Altorki, MD, Weill Medical College of Cornell University

Study Documents (Full-Text)

None provided.

More Information

Publications

• Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 Feb 2;92(3):205-16.

• Responsible Party: Ludwig Institute for Cancer Research
• ClinicalTrials.gov Identifier: NCT00199836
• Other Study ID Numbers: LUD2002-007
• First Posted: Sep 20, 2005
• Last Update Posted: Jul 15, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Ludwig Institute for Cancer Research: cancer vaccine; NY-ESO-1b peptide; CpG 7909; Montanide® ISA-51; LAGE-1; immune response; safety
• Additional relevant MeSH terms: Monatide (IMS 3015)

Study Results

Participant Flow

Arm/Group Title	Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen.
Arm/Group Description	NY-ESO-1b peptide, 100 μg mixed with 1 mg CpG 7909 and 0.5mL of Montanide® ISA-51 was administered to patients with cancer expressing NY-ESO-1 or LAGE-1 antigen. The injections were given subcutaneously beginning on week 1 and repeated every three weeks for 4 injections total. There was a 3 week follow-up period after the last injection. In the absence of toxicity and progressive disease (PD), a second cycle was offered to patients who received 4 vaccinations.
Period Title: Overall Study
STARTED	14
COMPLETED	8
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen.
Arm/Group Description	NY-ESO-1b peptide, 100 μg mixed with 1 mg CpG 7909 and 0.5mL of Montanide® ISA-51 was administered to patients with cancer expressing NY-ESO-1 or LAGE-1 antigen. The injections were given subcutaneously beginning on week 1 and repeated every three weeks for 4 injections total. There was a 3 week follow-up period after the last injection. In the absence of toxicity and progressive disease (PD), a second cycle was offered to patients who received 4 vaccinations.
Overall Participants	14
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	11 78.6%
>=65 years	3 21.4%
Sex: Female, Male (Count of Participants)
Female	8 57.1%
Male	6 42.9%
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	14 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
Germany	11 78.6%
United States	3 21.4%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With NY-ESO-1 Specific Humoral Immunity as Determined by an Increase in Antibody Titer From Baseline.
Description	Blood samples were obtained at baseline (prior to the first dose), prior to the second, third and fourth injection and 2 weeks after the fourth injection in both cycles 1 and 2 for the assessment of NY-ESO-1 specific antibodies by an enzyme-linked immunosorbent assay (ELISA). A positive response was a readable optical density at 280 nm.
Time Frame	up to 27 weeks

Outcome Measure Data

Analysis Population Description

All patients who received at least one dose of NY-ESO-1b peptide, 100 μg mixed with 1 mg CpG 7909 and 0.5mL of Montanide® ISA-51 and had pre- and post-treatment samples taken.

Arm/Group Title	Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen.
Arm/Group Description	NY-ESO-1b peptide, 100 μg mixed with 1 mg CpG 7909 and 0.5mL of Montanide® ISA-51 was administered to patients with cancer expressing NY-ESO-1 or LAGE-1 antigen. The injections were given subcutaneously beginning on week 1 and repeated every three weeks for 4 injections total. There was a 3 week follow-up period after the last injection. In the absence of toxicity and PD, a second cycle was offered to patients who received 4 vaccinations.
Measure Participants	14
Number of patients with negative titers both pre- and post-treatment	8 57.1%
Number of patients with positive titers both pre- and post-treatment	5 35.7%
Number of patients with negative titers at baseline and positive titers after treatment	1 7.1%

2. Primary Outcome

Title	Number of Patients With NY-ESO-1 Specific Cellular Immunity as Measured by an Increase in NY-ESO-1b Specific CD8+ T-cells Following Treatment.
Description	Blood samples were obtained at baseline, prior to the second, third and fourth injection and 2 weeks after the fourth injection in both cycles 1 and 2 for the assessment of NY-ESO-1b specific CD8+ T-cells by ELISPOT assays.
Time Frame	up to 27 weeks

Outcome Measure Data

Analysis Population Description

All patients who received at least one dose of NY-ESO-1b peptide, 100 μg mixed with 1 mg CpG 7909 and 0.5mL of Montanide® ISA-51 and had pre- and post-treatment samples taken were included in the Cycle 1 results. Cycle 2 results include all patients who received Cycle 2 treatment.

Arm/Group Title	Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen.
Arm/Group Description	NY-ESO-1b peptide, 100 μg mixed with 1 mg CpG 7909 and 0.5mL of Montanide® ISA-51 was administered to patients with cancer expressing NY-ESO-1 or LAGE-1 antigen. The injections were given subcutaneously beginning on week 1 and repeated every three weeks for 4 injections total. There was a 3 week follow-up period after the last injection. In the absence of toxicity and PD, a second cycle was offered to patients who received 4 vaccinations.
Measure Participants	14
Number of patients with an increase in NY-ESO-1b specific CD8+ T-cells during cycle 1	4 28.6%
Number of patients without an increase in NY-ESO-1b specific CD8+ T-cells during cycle 1	10 71.4%
Number of patients with an increase in NY-ESO-1b specific CD8+ T-cells during cycle 2	5 35.7%

3. Primary Outcome

Title	Number of Patients With Delayed-Type Hypersensitivity (DTH) Skin Reactions to NY-ESO-1b Peptide
Description	10 mcg NY-ESO-1b peptide was injected intradermally at a separate site from the vaccination at baseline and after the second and fourth injection of each cycle. Assessment of DTH reactions as evidenced by redness and induration was performed 48 h after injection. The number of patients with DTH positive skin reactions was reported at each timepoint.
Time Frame	up to 25 weeks

Outcome Measure Data

Analysis Population Description

All patients who received at least one dose of NY-ESO-1b peptide, 100 μg mixed with 1 mg CpG 7909 and 0.5mL of Montanide® ISA-51 and had pre- and post-treatment assessments at the given timeframes. One patient did not have post-injection DTH testing.

Arm/Group Title	Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen.
Arm/Group Description	NY-ESO-1b peptide, 100 μg mixed with 1 mg CpG 7909 and 0.5mL of Montanide® ISA-51 was administered to patients with cancer expressing NY-ESO-1 or LAGE-1 antigen. The injections were given subcutaneously beginning on week 1 and repeated every three weeks for 4 injections total. There was a 3 week follow-up period after the last injection. In the absence of toxicity and PD, a second cycle was offered to patients who received 4 vaccinations.
Measure Participants	14
Number of Patients With DTH Skin Reactions	2 14.3%
Number of Patients Without DTH Skin Reactions	12 85.7%
Number of Patients With DTH Skin Reactions	0 0%
Number of Patients Without DTH Skin Reactions	13 92.9%
Number of Patients With DTH Skin Reactions	1 7.1%
Number of Patients Without DTH Skin Reactions	7 50%
Number of Patients With DTH Skin Reactions	3 21.4%
Number of Patients Without DTH Skin Reactions	2 14.3%
Number of Patients With DTH Skin Reactions	1 7.1%
Number of Patients Without DTH Skin Reactions	4 28.6%

4. Primary Outcome

Title	Safety as Measured by the Number of Patients With Dose Limiting Toxicities (DLT)
Description	DLT was defined as the following toxicities definitely, probably, or possibly related to the administration of NY-ESO-1b peptide, 100 μg mixed with 1 mg CpG 7909 and 0.5mL of Montanide® ISA-51: ≥ Grade 2 autoimmune phenomena Asymptomatic bronchospasm or generalized urticaria ≥ Grade 3 hematological and non hematological toxicities.
Time Frame	up to 28 weeks

Outcome Measure Data

Analysis Population Description

All patients who received at least one dose of NY-ESO-1b peptide, 100 μg mixed with 1 mg CpG 7909 and 0.5mL of Montanide® ISA-51.

Arm/Group Title	Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen.
Arm/Group Description	NY-ESO-1b peptide, 100 μg mixed with 1mg CpG 7909 and 0.5mL of Montanide® ISA-51 was administered to patients with cancer expressing NY-ESO-1 or LAGE-1 antigen. The injections were given subcutaneously beginning on week 1 and repeated every three weeks for 4 injections total. There was a 3 week follow-up period after the last injection. In the absence of toxicity and PD, a second cycle was offered to patients who received 4 vaccinations.
Measure Participants	14
Count of Participants [Participants]	0 0%

5. Secondary Outcome

Title	Number of Patients With Tumor Responses as Measured by the Response Evaluation Criteria in Solid Tumors (RECIST)
Description	Computed tomography (CT) scans were performed at screening, and during weeks 13 and 28. Response was assessed using RECIST version 1.0 (Therasse et al, J Natl Cancer Inst 2000; 92:205-16). 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. No evidence of disease (NED): no target or non-target lesions at baseline and no new lesions identified on post-baseline scans.
Time Frame	up to 28 weeks

Outcome Measure Data

Analysis Population Description

All patients who received at least one dose of NY-ESO-1b peptide, 100 μg mixed with 1 mg CpG 7909 and 0.5mL of Montanide® ISA-51 and had at least one tumor response assessment.

Arm/Group Title	Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen.
Arm/Group Description	NY-ESO-1b peptide, 100 μg mixed with 1 mg CpG 7909 and 0.5mL of Montanide® ISA-51 was administered to patients with cancer expressing NY-ESO-1 or LAGE-1 antigen. The injections were given subcutaneously beginning on week 1 and repeated every three weeks for 4 injections total. There was a 3 week follow-up period after the last injection. In the absence of toxicity and PD, a second cycle was offered to patients who received 4 vaccinations.
Measure Participants	14
Stable Disease	3 21.4%
Complete Response	0 0%
Partial Response	0 0%
No Evidence of Disease	2 14.3%
Progressive Disease	9 64.3%

Adverse Events

Time Frame	Up to 28 weeks.
Adverse Event Reporting Description	All adverse events (AEs) occurring after signed informed consent were to be documented in the source records and on the respective AE case report form (CRF), regardless of causal relationship. Toxicity was evaluated according to the National Cancer Institute CTCAE Scale (Version 3.0).
Arm/Group Title	Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen.
Arm/Group Description	NY-ESO-1b peptide, 100 μg mixed with 1 mg CpG 7909 and 0.5mL of Montanide® ISA-51 was administered to patients with cancer expressing NY-ESO-1 or LAGE-1 antigen. The injections were given subcutaneously beginning on week 1 and repeated every three weeks for 4 injections total. There was a 3 week follow-up period after the last injection of peptide. In the absence of toxicity and PD, a second cycle was offered to patients who received 4 vaccinations.
All Cause Mortality
	Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen.
	Affected / at Risk (%)	# Events
Total	2/14 (14.3%)
Serious Adverse Events
	Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen.
	Affected / at Risk (%)	# Events
Total	6/14 (42.9%)
Cardiac disorders
Angina pectoris	1/14 (7.1%)
Cardiac failure	1/14 (7.1%)
Tachyarrhythmia	1/14 (7.1%)
Gastrointestinal disorders
Pancreatitis	1/14 (7.1%)
Gastroenteritis	1/14 (7.1%)
General disorders
Asthenia	1/14 (7.1%)
Hepatobiliary disorders
Cholecystitis	1/14 (7.1%)
Injury, poisoning and procedural complications
Overdose	1/14 (7.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain metastases	1/14 (7.1%)
Nervous system disorders
Convulsion	1/14 (7.1%)
Other (Not Including Serious) Adverse Events
	Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen.
	Affected / at Risk (%)	# Events
Total	14/14 (100%)
Blood and lymphatic system disorders
Anemia	3/14 (21.4%)
Cardiac disorders
Dyspnea exertional	1/14 (7.1%)
Sinus tachycardia	1/14 (7.1%)
Gastrointestinal disorders
Abdominal pain	2/14 (14.3%)
Ascites	1/14 (7.1%)
Dyspepsia	1/14 (7.1%)
Gastric ulcer	1/14 (7.1%)
Gastrointestinal infection	2/14 (14.3%)
Nausea	3/14 (21.4%)
General disorders
Application site eczema	1/14 (7.1%)
Axillary pain	1/14 (7.1%)
Brain edema	1/14 (7.1%)
Chills	4/14 (28.6%)
Fatigue	3/14 (21.4%)
Flu-like symptoms	4/14 (28.6%)
Hypothermia	2/14 (14.3%)
Inflammation	1/14 (7.1%)
Injection site induration	2/14 (14.3%)
Injection site reaction	4/14 (28.6%)
Pain	2/14 (14.3%)
Pyrexia	4/14 (28.6%)
Hepatobiliary disorders
Gamma glutamyl transferase elevated	1/14 (7.1%)
Hepatomegaly	1/14 (7.1%)
Infections and infestations
Herpes simplex	1/14 (7.1%)
Urinary tract infection	2/14 (14.3%)
Injury, poisoning and procedural complications
Thermal burn	1/14 (7.1%)
Investigations
Blood lactate dehydrogenase increased	1/14 (7.1%)
Karnofsky scale worsened	1/14 (7.1%)
Weight decreased	1/14 (7.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/14 (7.1%)
Back pain	3/14 (21.4%)
Hypertonia	1/14 (7.1%)
Myalgia	1/14 (7.1%)
Nervous system disorders
Headache	2/14 (14.3%)
Trigeminal neuralgia	1/14 (7.1%)
Psychiatric disorders
Depression	1/14 (7.1%)
Restlessness	1/14 (7.1%)
Sleep disturbance	1/14 (7.1%)
Respiratory, thoracic and mediastinal disorders
Nasopharyngitis	4/14 (28.6%)
Pharyngolaryngeal pain	1/14 (7.1%)
Upper respiratory tract infection	2/14 (14.3%)
Wheezes	1/14 (7.1%)
Skin and subcutaneous tissue disorders
Eczema	1/14 (7.1%)
Surgical and medical procedures
Catheter placement	1/14 (7.1%)
Resection of metastasis	2/14 (14.3%)
Vascular disorders
Hypotension	1/14 (7.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.