Cancer, Neoplasm
Conditions
Keywords
cancer vaccine, NY-ESO-1b peptide, CpG 7909, Montanide® ISA-51, LAGE-1, immune response, safety
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.
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.
Interventions
BIOLOGICALNY-ESO-1b peptide plus CpG 7909 and Montanide® ISA-51
Sponsors
Ludwig Institute for Cancer Research
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Progressive Disease | 5 |
Baseline characteristics
| Characteristic | Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen. |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 11 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 | 14 Participants |
| Region of Enrollment Germany | 11 participants |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 14 |
| other Total, other adverse events | 14 / 14 |
| serious Total, serious adverse events | 6 / 14 |
Outcome results
Primary
Number of Patients With Delayed-Type Hypersensitivity (DTH) Skin Reactions to NY-ESO-1b Peptide
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
Population: 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 | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen. | Number of Patients With Delayed-Type Hypersensitivity (DTH) Skin Reactions to NY-ESO-1b Peptide | Baseline | Number of Patients With DTH Skin Reactions | 2 Participants |
| Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen. | Number of Patients With Delayed-Type Hypersensitivity (DTH) Skin Reactions to NY-ESO-1b Peptide | Baseline | Number of Patients Without DTH Skin Reactions | 12 Participants |
| Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen. | Number of Patients With Delayed-Type Hypersensitivity (DTH) Skin Reactions to NY-ESO-1b Peptide | Week 4 | Number of Patients With DTH Skin Reactions | 0 Participants |
| Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen. | Number of Patients With Delayed-Type Hypersensitivity (DTH) Skin Reactions to NY-ESO-1b Peptide | Week 4 | Number of Patients Without DTH Skin Reactions | 13 Participants |
| Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen. | Number of Patients With Delayed-Type Hypersensitivity (DTH) Skin Reactions to NY-ESO-1b Peptide | Week 10 | Number of Patients With DTH Skin Reactions | 1 Participants |
| Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen. | Number of Patients With Delayed-Type Hypersensitivity (DTH) Skin Reactions to NY-ESO-1b Peptide | Week 10 | Number of Patients Without DTH Skin Reactions | 7 Participants |
| Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen. | Number of Patients With Delayed-Type Hypersensitivity (DTH) Skin Reactions to NY-ESO-1b Peptide | Week 19 | Number of Patients With DTH Skin Reactions | 3 Participants |
| Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen. | Number of Patients With Delayed-Type Hypersensitivity (DTH) Skin Reactions to NY-ESO-1b Peptide | Week 19 | Number of Patients Without DTH Skin Reactions | 2 Participants |
| Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen. | Number of Patients With Delayed-Type Hypersensitivity (DTH) Skin Reactions to NY-ESO-1b Peptide | Week 25 | Number of Patients With DTH Skin Reactions | 1 Participants |
| Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen. | Number of Patients With Delayed-Type Hypersensitivity (DTH) Skin Reactions to NY-ESO-1b Peptide | Week 25 | Number of Patients Without DTH Skin Reactions | 4 Participants |
Primary
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.
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
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen. | 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. | Number of patients with an increase in NY-ESO-1b specific CD8+ T-cells during cycle 2 | 5 Participants |
| Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen. | 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. | Number of patients with an increase in NY-ESO-1b specific CD8+ T-cells during cycle 1 | 4 Participants |
| Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen. | 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. | Number of patients without an increase in NY-ESO-1b specific CD8+ T-cells during cycle 1 | 10 Participants |
Primary
Number of Patients With NY-ESO-1 Specific Humoral Immunity as Determined by an Increase in Antibody Titer From Baseline.
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
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen. | Number of Patients With NY-ESO-1 Specific Humoral Immunity as Determined by an Increase in Antibody Titer From Baseline. | Number of patients with positive titers both pre- and post-treatment | 5 Participants |
| Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen. | Number of Patients With NY-ESO-1 Specific Humoral Immunity as Determined by an Increase in Antibody Titer From Baseline. | Number of patients with negative titers at baseline and positive titers after treatment | 1 Participants |
| Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen. | Number of Patients With NY-ESO-1 Specific Humoral Immunity as Determined by an Increase in Antibody Titer From Baseline. | Number of patients with negative titers both pre- and post-treatment | 8 Participants |
Primary
Safety as Measured by the Number of Patients With Dose Limiting Toxicities (DLT)
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
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen. | Safety as Measured by the Number of Patients With Dose Limiting Toxicities (DLT) | 0 Participants |
Secondary
Number of Patients With Tumor Responses as Measured by the Response Evaluation Criteria in Solid Tumors (RECIST)
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
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen. | Number of Patients With Tumor Responses as Measured by the Response Evaluation Criteria in Solid Tumors (RECIST) | Stable Disease | 3 Participants |
| Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen. | Number of Patients With Tumor Responses as Measured by the Response Evaluation Criteria in Solid Tumors (RECIST) | Complete Response | 0 Participants |
| Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen. | Number of Patients With Tumor Responses as Measured by the Response Evaluation Criteria in Solid Tumors (RECIST) | Partial Response | 0 Participants |
| Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen. | Number of Patients With Tumor Responses as Measured by the Response Evaluation Criteria in Solid Tumors (RECIST) | No Evidence of Disease | 2 Participants |
| Patients With Cancer Expressing NY-ESO-1 or LAGE-1 Antigen. | Number of Patients With Tumor Responses as Measured by the Response Evaluation Criteria in Solid Tumors (RECIST) | Progressive Disease | 9 Participants |