Cancer
Conditions
Keywords
Cancer, Vaccine, Oncology, Malignancies, Wilms' Tumor, WT1, Ovarian, Glioblastoma [GBM], Acute myeloid leukemia [AML]
Brief summary
This clinical study is designed to evaluate the safety, immunogenicity and antitumor activity of WT2725. WT2725 will be administered to patients with advanced malignancies known to overexpress WT1
Detailed description
Treatment with other WT1 vaccines in clinical trials has shown evidence of immunogenicity and clinical response in various malignancies. This study will assist with determining which dose level(s) to use in future clinical studies and will evaluate both clinical and immunological response.
Interventions
BIOLOGICALWT2725
WT2725 injection Study drug will be administered every 1-4 weeks
Sponsors
Sumitomo Pharma Co., Ltd.
Sumitomo Pharma America, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Part 1 Inclusion Criteria: * Patient must have an Eastern Cooperative Oncology Group (ECOG) Performance Score of 0, 1, or 2 * Patient must have one of the following histologically or cytologically documented measurable (may be measureable by tumor markers only, such as quantitative RT-PCR for WT1 transcript for AML, or CA-125 for ovarian carcinoma) advanced stage malignancies: non-small cell lung, ovarian, glioblastoma, and AML (not including acute promyelocytic leukemia), known to overexpress the WT1 protein. * Patient must qualify with a study specific HLA typing assay. * Haematological parameters: * Absolute neutrophil count (ANC) ≥ 1,000/μl * Platelet count ≥ 10.0x10(to the 4th power)/μl (≥ 5.0 x 10(to 4th power)/μl after stem cell transplant) * Hemoglobin ≥ 9.0 g/dL * Absolute lymphocyte count (ALC) ≥ 1,000/μl (≥ 500/μl after stem cell transplant) Note: After completion of dose escalation, patients with AML are not required to meet these hematologic criteria. * Biochemical Parameters: * serum creatinine of ≤ 1.5x upper limit of normal (ULN) for the reference lab. * total bilirubin of ≤ 2.0 mg/dl (≤ 3.0 mg/dl for patients with known Gilbert's syndrome) * alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 times the ULN for the reference lab * Patient must have access to archival tumor tissue sample or agree to undergo biopsy after study eligibility has been confirmed to obtain fresh sample for evaluation of WT1 expression. In place of archival tumor tissue samples, subjects with AML should have available a bone marrow aspirate and/or, bone marrow biopsy, with PCR for WT1 transcript performed before the first dose of study drug. Note: The archived tumor tissue sample does not need to be delivered to the clinical site prior to enrollment of the patient, however its availability should be confirmed through provision of the accession number or other identification number. Patient Inclusion Criteria - Part 2: * Patient or his or her legal representatives must give written informed consent and privacy authorization prior to participation in the study. * Patient must be willing and able to comply with the study procedures and visit schedules and must be able to follow verbal and written instructions. * Patient must be ≥ 18 years of age. * Women of childbearing potential and men with female sexual partners of childbearing potential must agree to abstain from sexual intercourse or use a double barrier method to determine if a woman is of childbearing potential (http://www.nccn.org/professionals/physician\_gls/f\_guidelines.asp). * Patient must have an ECOG Performance Score of 0, 1, or 2 (refer to Appendix II). * Patient has a life expectancy of at least 4 months. * Patient must have histologically or cytologically documented measurable (may be measurable by tumor markers only, such as quantitative RT-PCR for WT1 transcript for AML) advanced stage glioblastoma or AML (not including acute promyelocytic leukemia), known to overexpress the WT1 protein. Note: Determination of WT1 expression will not be assessed prior to patient enrollment. * Patient must have an advanced stage malignancy defined as meeting at least one of the following criteria: * progressed or recurred despite standard therapy * no standard therapy exists * patient is intolerant of standard therapy * patient is not a candidate for standard therapy * Patient must be HLA-A\*0201+ and/or HLA-A\*0206+ * Patient with glioblastoma must have adequate bone marrow and immune reserve, as documented by: * ANC ≥ 1000/μl (≥ 500/μl after stem cell transplant) * Platelet count ≥ 10.0 x 1(to the 4th power)/μl (≥ 5.0 x 10(to the 4th power)/μl after stem cell transplant) * Hemoglobin ≥ 9.0 g/dL * ALC ≥ 900/μl (Note: Patients with AML are not required to meet these hematologic criteria). * Patient must have adequate renal function documented by a serum creatinine of ≤ 1.5 times the ULN for the reference lab. * Patient must have adequate hepatic function documented by a total bilirubin of ≤ 2.0 mg/dl (≤ 3.0 mg/dl for patients with known Gilbert's syndrome) and ALT and AST ≤ 3 times the ULN for the reference lab. * Patient must have access to archival tumor tissue sample or agree to undergo biopsy after study eligibility has been confirmed to obtain fresh sample for evaluation of WT1 expression. In place of archival tumor tissue samples, patients with AML should have available a bone marrow aspirate and/or bone marrow biopsy with PCR for WT1 transcript performed before the first dose of study drug. Note: The archived tumor tissue sample does not need to be delivered to the clinical site prior to enrollment of the patient, however its availability should be confirmed through provision of the accession number or other identification number. • Patients with AML must be willing to undergo bone marrow aspiration/biopsy during treatment if there are no other indicators of measureable disease. Part 1
Exclusion criteria
* Patient with an extensively disseminated primary glioblastoma. * Patient with symptomatic brain metastases, ie, not neurologically stable or requiring treatment with corticosteroids, or central nervous system (CNS) leukemia. * Patient with an infection requiring treatment with systemic antibiotics or antiviral medication or has completed treatment for such an infection within 4 days prior to planned initial dose of WT2725. * Patient requiring systemic, pharmacologic doses of corticosteroids (equivalent to \> 60 mg hydrocortisone/day or 2 mg dexamethasone/day). Replacement doses (equivalent to ≤ 5 mg prednisone/day), and topical, ophthalmic, and inhalation steroids are permitted as needed. * Patient has a positive test for Hepatitis B surface antigen, Hepatitis C antibody, human immunodeficiency virus (HIV)-1, or HIV-2 antibody, or has a history of a positive result. * Patient has received any of the following treatments within the specified timeframe prior to dosing: * endocrine therapy, immunotherapy, transfusion, hematopoietic factors within 14 days prior to planned first dose of study drug (Note: After completion of dose escalation, patients with AML are not required to meet these hematologic criteria, eg. transfusions and hematopoietic growth factors.) * chemotherapy including molecular-targeting therapy within 21 days (for molecular-targeted agents that are not associated with myelosuppression or immunosuppression, the minimum interval is 5 half-lives if that is less than 21 days) * surgery, radiation, or immunosuppressants within 28 days * investigational drug within 28 days * mitomycin-C or nitrosoureas within 42 days * Patient with an unresolved ≥ Grade 2 AE from a previous antineoplastic treatment, excluding alopecia. * Pregnant or lactating women * Patient with an autoimmune condition * Patients with serious unstable medical illness * Patient with pleural effusion, ascites, or pericardial fluid requiring drainage. * Patient is a staff member of the sponsor or clinical site and is involved in the conduct of the study or the relative of such a staff member. Patient
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Dose-limiting Toxicities and Adverse Events | Up to 4 months | Evaluation of the safety and tolerability of WT2725 Dosing Emulsion based on the occurrence of DLT and AEs The safety and tolerability of WT2725 Dosing Emulsion will be evaluated based on the occurrence of DLT and AEs, and the findings from clinical laboratory tests, vital signs measurements, body weight measurements, and electrocardiogram (ECG) results. The incidence of DLT will be evaluated during the DLT Evaluation Period, which extends from the day of the first dose to just prior to the fifth dose of study drug (Days 1 to 29). No more than 4 doses of study drug will be administered during the DLT Evaluation Period. |
| Maximum Tolerated Dose (MTD) of WT2725 Based on the Evaluation of Dose-limiting Toxicity (DLT) | Day 1 - Day 29 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Antitumor Responses to WT2725 Based on the Immune-related Response Criteria (irRC) | Day 1 - within 28 days after last dose | Tumor response, as evaluated according to irRC, was based on total measurable tumor burden in patients with solid tumors (ie, non-AML patients). Tumor assessments will be conducted during screening, and then every 8 weeks after the first dose of study drug. All tumor assessments may be performed within ±7 days of the scheduled assessment. All patients should complete an End of Study visit within 28 days after the last dose of study drug and prior to the start of alternate antineoplastic therapy. |
| Immune Response to WT2725 | Day 1 - within 28 days after last dose | The modified IWG response criteria were used to assess drug activity in AML patients. Tumor assessments will be conducted during screening, and then every 8 weeks after the first dose of study drug. All tumor assessments may be performed within ±7 days of the scheduled assessment. All patients should complete an End of Study visit within 28 days after the last dose of study drug and prior to the start of alternate antineoplastic therapy. |
Countries
United States
Participant flow
Pre-assignment details
please note that there were two subjects that never received study drug medication
Participants by arm
| Arm | Count |
|---|---|
| WT2725 0.3 mg WT2725; injection WT2725: WT2725 injection Study drug will be administered every 1-4 weeks | 5 |
| WT2725 0.9 mg WT2725; injection WT2725: WT2725 injection Study drug will be administered every 1-4 weeks | 5 |
| WT2725 3.0 mg WT2725; injection WT2725: WT2725 injection Study drug will be administered every 1-4 weeks | 6 |
| WT2725 9 mg WT2725; injection WT2725: WT2725 injection Study drug will be administered every 1-4 weeks | 28 |
| WT2725 18 mg WT2725; injection WT2725: WT2725 injection Study drug will be administered every 1-4 weeks | 9 |
| WT2725 27 mg WT2725; injection WT2725: WT2725 injection Study drug will be administered every 1-4 weeks | 9 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 3 | 0 | 0 |
| Overall Study | Death | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 1 | 13 | 3 | 1 |
| Overall Study | progression/treatment failure | 2 | 4 | 3 | 7 | 3 | 5 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | study stopped by sponsor | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 1 | 3 | 3 | 3 |
Baseline characteristics
| Characteristic | WT2725 0.3 mg | WT2725 0.9 mg | WT2725 3.0 mg | WT2725 9 mg | WT2725 18 mg | WT2725 27 mg | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 2 Participants | 13 Participants | 2 Participants | 4 Participants | 24 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 3 Participants | 4 Participants | 15 Participants | 7 Participants | 5 Participants | 38 Participants |
| Age, Continuous | 59.4 years STANDARD_DEVIATION 8.96 | 62.6 years STANDARD_DEVIATION 7.99 | 63.0 years STANDARD_DEVIATION 9.25 | 57.5 years STANDARD_DEVIATION 15.46 | 51.3 years STANDARD_DEVIATION 16.14 | 59.4 years STANDARD_DEVIATION 15.83 | 58.0 years STANDARD_DEVIATION 14.17 |
| ECOG Performance Status [n(%)] The Eastern Cooperative Oncology Group (ECOG) score 0 | 1 Participants | 2 Participants | 6 Participants | 11 Participants | 1 Participants | 3 Participants | 24 Participants |
| ECOG Performance Status [n(%)] The Eastern Cooperative Oncology Group (ECOG) score 1 | 4 Participants | 3 Participants | 0 Participants | 16 Participants | 8 Participants | 5 Participants | 36 Participants |
| ECOG Performance Status [n(%)] The Eastern Cooperative Oncology Group (ECOG) score 2 | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| ECOG Performance Status [n(%)] The Eastern Cooperative Oncology Group (ECOG) score 3 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| ECOG Performance Status [n(%)] The Eastern Cooperative Oncology Group (ECOG) score 4 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 4 Participants | 5 Participants | 27 Participants | 9 Participants | 8 Participants | 57 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 3 Participants | 3 Participants | 5 Participants | 27 Participants | 8 Participants | 7 Participants | 53 Participants |
| Region of Enrollment United States | 5 Participants | 5 Participants | 6 Participants | 28 Participants | 9 Participants | 9 Participants | 62 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 6 Participants | 17 Participants | 2 Participants | 1 Participants | 33 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 0 Participants | 11 Participants | 7 Participants | 8 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 | 0 / 6 | 0 / 28 | 0 / 9 | 0 / 9 |
| other Total, other adverse events | 0 / 5 | 0 / 5 | 0 / 6 | 0 / 28 | 0 / 9 | 0 / 9 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 | 1 / 6 | 8 / 28 | 3 / 9 | 5 / 9 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) of WT2725 Based on the Evaluation of Dose-limiting Toxicity (DLT)
Time frame: Day 1 - Day 29
Population: Safety Population (defined as all enrolled patients who received at least one dose of study drug.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| WT2725 0.3 mg | Maximum Tolerated Dose (MTD) of WT2725 Based on the Evaluation of Dose-limiting Toxicity (DLT) | 0 Dose Limiting Toxicity |
| WT2725 0.9 mg | Maximum Tolerated Dose (MTD) of WT2725 Based on the Evaluation of Dose-limiting Toxicity (DLT) | 0 Dose Limiting Toxicity |
| WT2725 3.0 mg | Maximum Tolerated Dose (MTD) of WT2725 Based on the Evaluation of Dose-limiting Toxicity (DLT) | 0 Dose Limiting Toxicity |
| WT2725 9 mg | Maximum Tolerated Dose (MTD) of WT2725 Based on the Evaluation of Dose-limiting Toxicity (DLT) | 0 Dose Limiting Toxicity |
| WT2725 18 mg | Maximum Tolerated Dose (MTD) of WT2725 Based on the Evaluation of Dose-limiting Toxicity (DLT) | 0 Dose Limiting Toxicity |
| WT2725 27 mg | Maximum Tolerated Dose (MTD) of WT2725 Based on the Evaluation of Dose-limiting Toxicity (DLT) | 0 Dose Limiting Toxicity |
Comparison: The MTD could not be established for this study as no DLTs occurred at doses up to and including 27.0 mg
Primary
Occurrence of Dose-limiting Toxicities and Adverse Events
Evaluation of the safety and tolerability of WT2725 Dosing Emulsion based on the occurrence of DLT and AEs The safety and tolerability of WT2725 Dosing Emulsion will be evaluated based on the occurrence of DLT and AEs, and the findings from clinical laboratory tests, vital signs measurements, body weight measurements, and electrocardiogram (ECG) results. The incidence of DLT will be evaluated during the DLT Evaluation Period, which extends from the day of the first dose to just prior to the fifth dose of study drug (Days 1 to 29). No more than 4 doses of study drug will be administered during the DLT Evaluation Period.
Time frame: Up to 4 months
Population: Safety Population (defined as all enrolled patients who received at least one dose of study drug.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| WT2725 0.3 mg | Occurrence of Dose-limiting Toxicities and Adverse Events | 0 number of occurances |
| WT2725 0.9 mg | Occurrence of Dose-limiting Toxicities and Adverse Events | 0 number of occurances |
| WT2725 3.0 mg | Occurrence of Dose-limiting Toxicities and Adverse Events | 0 number of occurances |
| WT2725 9 mg | Occurrence of Dose-limiting Toxicities and Adverse Events | 0 number of occurances |
| WT2725 18 mg | Occurrence of Dose-limiting Toxicities and Adverse Events | 0 number of occurances |
| WT2725 27 mg | Occurrence of Dose-limiting Toxicities and Adverse Events | 0 number of occurances |
Secondary
Antitumor Responses to WT2725 Based on the Immune-related Response Criteria (irRC)
Tumor response, as evaluated according to irRC, was based on total measurable tumor burden in patients with solid tumors (ie, non-AML patients). Tumor assessments will be conducted during screening, and then every 8 weeks after the first dose of study drug. All tumor assessments may be performed within ±7 days of the scheduled assessment. All patients should complete an End of Study visit within 28 days after the last dose of study drug and prior to the start of alternate antineoplastic therapy.
Time frame: Day 1 - within 28 days after last dose
Population: Efficacy irRC population: including all the patients in the Safety population who are not AML patients and whose lesions are measureable and have at least one posttreatment assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| WT2725 0.3 mg | Antitumor Responses to WT2725 Based on the Immune-related Response Criteria (irRC) | 0 participants |
| WT2725 0.9 mg | Antitumor Responses to WT2725 Based on the Immune-related Response Criteria (irRC) | 0 participants |
| WT2725 3.0 mg | Antitumor Responses to WT2725 Based on the Immune-related Response Criteria (irRC) | 0 participants |
| WT2725 9 mg | Antitumor Responses to WT2725 Based on the Immune-related Response Criteria (irRC) | 2 participants |
| WT2725 18 mg | Antitumor Responses to WT2725 Based on the Immune-related Response Criteria (irRC) | 0 participants |
| WT2725 27 mg | Antitumor Responses to WT2725 Based on the Immune-related Response Criteria (irRC) | 1 participants |
Secondary
Immune Response to WT2725
The modified IWG response criteria were used to assess drug activity in AML patients. Tumor assessments will be conducted during screening, and then every 8 weeks after the first dose of study drug. All tumor assessments may be performed within ±7 days of the scheduled assessment. All patients should complete an End of Study visit within 28 days after the last dose of study drug and prior to the start of alternate antineoplastic therapy.
Time frame: Day 1 - within 28 days after last dose
Population: Efficacy population for modified IWG response: includes all the AML patients in the Safety population who have \>5% marrow blasts or \>50 copy/μｇRNA of quantitative RT-PCR for WT1 transcript before the first date/time of study drug and who have at least one posttreatment assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| WT2725 9 mg | Immune Response to WT2725 | 3 participants |
| WT2725 18 mg | Immune Response to WT2725 | 2 participants |
| WT2725 27 mg | Immune Response to WT2725 | 0 participants |