B-cell Non-Hodgkin Lymphoma
Conditions
Keywords
NHL, Immunocytokine, Lymphoma, Non-Hodgkin, B-cell, IL (interleukin)
Brief summary
This dose-escalation study is designed for determining the safety, tolerability, pharmacokinetics (PK), biological, and clinical activity of DI-Leu16-IL2 administered to participants with cluster of differentiation 20 (CD20) positive NHL that have failed standard rituximab-containing therapy.
Detailed description
The participants will be enrolled during dose escalation and during 2 expansion cohorts of up to 12 participants each. The dose escalation portion of the trial will incorporate a modified accelerated titration design. Therefore, the trial will enroll 3 participants per dose level with a doubling of the dose at each level during the accelerated stage of the study (skipping every other dose level). Once the first instance of any Grade 3 or higher treatment related toxicity (with some notable exceptions) is observed on the first cycle, the accelerated stage will end and the trial will revert to a conventional design using cohorts of 3 or 6 participants (standard 3+3 design), with single step 2 milligrams (mg)/square meter (m\^2) increments. To further explore the clinical efficacy, additional participants (up to 12 per cohort) may be enrolled at the optimal biologic dose (OBD) or maximum tolerated dose (MTD). At the end of the study, participants may be enrolled into an open-label extension study (AO-101-EXT \[NCT02151903\]), at the discretion of the investigator.
Interventions
DRUGDI-Leu16-IL2
DI-Leu16-IL2 will be administered per dose and schedule specified in the arm.
Sponsors
Alopexx Oncology, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participants with CD20-expressing B-cell NHL that is relapsed or refractory to standard therapy. Chronic lymphocytic leukemia/small lymphocytic lymphoma with peripheral blood leukemia/lymphoma cells and high-grade lymphomas are excluded. 2. Participants must have received prior rituximab-containing therapy. 3. Evaluable disease. In the absence of lymphadenopathy, splenomegaly with defects or measurable extra-medullary disease is acceptable. 4. Participants who have received a prior autologous stem cell transplant are eligible if the transplant occurred \>6 months ago. 5. Participants who have received a prior allogeneic stem cell transplant are eligible if: 1. The transplant occurred \>6 months ago 2. There is no evidence of active graft versus host disease 3. Systemic immunosuppressive agents (including corticosteroids) have not been received for at least 8 weeks 6. Karnofsky performance scale ≥70% 7. Life expectancy ≥12 weeks 8. Adequate baseline functions: 1. Serum creatinine ≤1.5 mg/deciliter (dL) 2. Total white blood cell (WBC) count ≥3000/microliter (µL) or absolute neutrophil count (ANC) ≥1000/µL 3. Absolute lymphocyte count ≥0.75 \* 10\^3/µL 4. Platelet count ≥75,000/µL 5. Hematocrit ≥25% or hemoglobin ≥9 grams/100 milliliters (mL) 6. Alanine aminotransferase (ALT) \<2.5 \* upper limit of normal (ULN) 7. Aspartate aminotransferase (AST) \<2.5 \* ULN 8. Total bilirubin (TBili) \<1.5 \* ULN 9. Sodium, potassium, and phosphorus levels no worse than grade 1 10. Chest x-ray (CXR) or computed tomography (CT) within 4 weeks prior to Day 1 with no evidence of pulmonary congestion, pleural effusions, pulmonary fibrosis, or significant emphysema. If results are questionable, participants should have additional lung function testing to exclude clinically relevant restriction or obstruction. Participants must have a forced expiratory volume (FEV-1) and diffusing capacity of the lung for carbon monoxide (DLCO) of at least 65% and 50% of expected, respectively. 11. Electrocardiogram (12-lead ECG) QTc ≤480 millisecond (ms) 12. Cardiac stress test (for example, stress thallium scan, stress echocardiography) with normal results if participant is suspected to have coronary artery disease. 9. Participants participating in the study are to use adequate birth control measures (abstinence, oral contraceptives, barrier method with spermicide or surgical sterilization) during the study. Females of childbearing potential must have a negative serum pregnancy test on the days of dosing. A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (that is, has had menses at any time in the preceding 24 consecutive months). 10. Provide written informed consent prior to any screening procedures
Exclusion criteria
1. Evidence of central nervous system lymphoma or lymphomatous meningitis 2. Prior treatment with interleukin 2 (IL2) within the last 5 years 3. Type I hypersensitivity or anaphylactic reactions to murine proteins or to previous infusion of rituximab 4. Pregnant or lactating female 5. An immediate need for palliative radiotherapy or systemic corticosteroid therapy 6. Known intercurrent infections (including hepatitis C virus and human immunodeficiency virus or other conditions), or clinical evidence of these conditions 7. Actively infected with or chronic carriers of hepatitis B virus as demonstrated by positive hepatitis B core antibody or hepatitis B surface antigen. Participants who are seropositive only, that is, surface antibody positive \[HbsAb\], are permitted. 8. Other significant active infection. 9. Major surgery, chemotherapy, investigational agent, or radiation within 30 days of Day 1 10. Uncontrolled hypertension (diastolic greater to or equal to 100 millimeters of mercury \[mmHg\]) or hypotension (systolic less than or equal to 90 mmHg) 11. History of repeated and clinically relevant episodes of syncope or other paroxysmal, ventricular, or other significant arrhythmias 12. History of medically significant ascites requiring repetitive paracentesis 13. Previous diagnosis of autoimmune disease (Exceptions: participants with autoimmune thyroiditis or vitiligo may be enrolled) 14. Organ transplant recipient 15. History of prior therapy or a serious, uncontrolled medical disorder that in the Investigator's opinion would impair participation in the study 16. Known hypersensitivity to Tween-80 or human immunoglobulin 17. Legal incapacity or limited legal capacity 18. Participants with bulky lymph nodes (LNs) (≥10 centimeters \[cm\]) or marked splenomegaly (that is, extending into pelvis or crossing the midline). 19. Circulating levels of rituximab \>75.0 micrograms (µg)/mL
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of DI-Leu16-IL2 | First 2 cycles of treatment (each cycle = 21 days) | The MTD was determined based on toxicities from the first 2 cycles of treatment. The MTD was the highest dose tested with no more than 1 participant out of 6 experienced a dose-limiting toxicity (DLT). All non-hematologic adverse events (AEs) and all hematologic AEs of greater than Grade 3 were considered relevant to determining DLTs. DLTs included absolute lymphocyte count (ALC) Grade 3 and 4 (if ALC does not resolve to baseline grade according to Common Terminology Criteria for Adverse Events (CTCAE) v4 within 5 days post the final injection per cycle of DI-Leu16-IL2), and absolute neutrophil count (ANC) Grade 3 (If ANC does not resolve to at least Grade 2 within 5 days post the final injection per cycle of DI-Leu16-IL2) and Grade 4 (any). |
| Number of Participants With a DLT | First 2 cycles of treatment (each cycle = 21 days) | All non-hematologic AEs and all hematologic AEs of greater than Grade 3 were considered relevant to determining DLTs. DLTs included ALC Grade 3 and 4 (if ALC does not resolve to baseline grade according to CTCAE v4 within 5 days post the final injection per cycle of DI-Leu16-IL2), and ANC Grade 3 (If ANC does not resolve to at least Grade 2 within 5 days post the final injection per cycle of DI-Leu16-IL2) and Grade 4 (any). |
| Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | First dose of study drug until first appearance of CR, CRu, PR, SD, or PD (up to 6 months) | BOR included complete response (CR), unconfirmed CR (CRu), partial response (PR), stable disease (SD), and progressive disease (PD). CR: 1) Disappearance of all detectable clinical and radiological evidence of disease; 2) lymph nodes (LN) regressed to normal size; 3) other organs (spleen, liver, kidneys) that were enlarged before therapy must have decreased in size; 4) clear bone marrow (BM) infiltrate. CRu: must meet CR criteria 1 and 3, as well as ≥1 of following: residual LN mass \>1.5 cm in greatest transverse diameter; individual nodes that were previously confluent regressed by \>75% in sum of product diameters (SPD); or indeterminate BM. PR: 6 largest dominant nodes or nodal masses decreased by ≤50% in SPD; no increase in size of other nodes; liver or spleen; splenic and hepatic nodules regressed ≥50% in SPD; and no new disease. SD: less than a PR but not PD. PD: 50% increase from nadir in SPD of any abnormal node for PR or nonresponders and appearance of any new lesion. |
| Tumor Measurement: Percent Change From Baseline in Sum of Product of Diameters at the End of Study | Baseline, end of study (EOS) (up to approximately 3 years) | Sum of product diameters sums the product of the 2 tumor measurements on each lesion. If only 1 measurement was available, it was used as the longest length and the product of the lengths in the sum. Baseline value is the last non-missing measurement prior to receiving study drug injection. None of the participants were considered evaluable in 'DI-Leu16-IL2 0.5 mg/m\^2' arm for this outcome measure at the end of study, and therefore, data were not collected for that arm. |
| Tumor Measurement: Percent Change From Baseline in Sum of Longest Diameters at the End of Study | Baseline, EOS (up to approximately 3 years) | Sum of longest diameters is the sum of the longest measured length of each tumor lesion. Baseline value is the last non-missing measurement prior to receiving study drug injection. None of the participants were considered evaluable in 'DI-Leu16-IL2 0.5 mg/m\^2' arm for this outcome measure at the end of study, and therefore, data were not collected for that arm. |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Anti-DI-Leu16-IL2 Antibodies | First dose of study drug up to EOS (up to approximately 3 years) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DI-Leu16-IL2 0.5 mg/m^2 Participants received DI-Leu16-IL2 0.5 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle) for a total of 4 cycles. | 3 |
| DI-Leu16-IL2 1.0 mg/m^2 Participants received DI-Leu16-IL2 1.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle) for a total of 4 cycles. | 3 |
| DI-Leu16-IL2 2.0 mg/m^2 Participants received DI-Leu16-IL2 2.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle) for a total of 4 cycles. | 9 |
| DI-Leu16-IL2 4.0 mg/m^2 Participants received DI-Leu16-IL2 4.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle) for a total of 4 cycles. | 7 |
| DI-Leu16-IL2 6.0 mg/m^2 Participants received DI-Leu16-IL2 6.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle) for a total of 4 cycles. | 2 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Progressive disease | 2 | 0 | 3 | 5 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 2 | 1 | 1 |
Baseline characteristics
| Characteristic | DI-Leu16-IL2 1.0 mg/m^2 | DI-Leu16-IL2 2.0 mg/m^2 | DI-Leu16-IL2 4.0 mg/m^2 | DI-Leu16-IL2 0.5 mg/m^2 | DI-Leu16-IL2 6.0 mg/m^2 | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 66.7 years STANDARD_DEVIATION 14.84 | 64.0 years STANDARD_DEVIATION 11.55 | 59.6 years STANDARD_DEVIATION 9.61 | 51.3 years STANDARD_DEVIATION 12.22 | 57.5 years STANDARD_DEVIATION 13.44 | 60.9 years STANDARD_DEVIATION 11.49 |
| Sex: Female, Male Female | 1 Participants | 6 Participants | 0 Participants | 1 Participants | 2 Participants | 10 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 7 Participants | 2 Participants | 0 Participants | 14 Participants |
| Tumor Measurement: Sum of Longest of Diameters | 6.133 cm STANDARD_DEVIATION 4.3524 | 9.462 cm STANDARD_DEVIATION 5.4068 | 11.100 cm STANDARD_DEVIATION 5.1901 | 6.000 cm STANDARD_DEVIATION 3.0414 | 10.300 cm STANDARD_DEVIATION 5.6569 | 9.161 cm STANDARD_DEVIATION 4.9829 |
| Tumor Measurement: Sum of Product of Diameters | 12.21667 centimeters (cm) STANDARD_DEVIATION 12.110806 | 17.63953 centimeters (cm) STANDARD_DEVIATION 16.388997 | 27.95857 centimeters (cm) STANDARD_DEVIATION 22.005858 | 15.11667 centimeters (cm) STANDARD_DEVIATION 9.726296 | 27.86500 centimeters (cm) STANDARD_DEVIATION 10.896515 | 20.50816 centimeters (cm) STANDARD_DEVIATION 16.836733 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 9 | 0 / 7 | 0 / 2 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 9 / 9 | 7 / 7 | 2 / 2 |
| serious Total, serious adverse events | 0 / 3 | 2 / 3 | 1 / 9 | 3 / 7 | 1 / 2 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) of DI-Leu16-IL2
The MTD was determined based on toxicities from the first 2 cycles of treatment. The MTD was the highest dose tested with no more than 1 participant out of 6 experienced a dose-limiting toxicity (DLT). All non-hematologic adverse events (AEs) and all hematologic AEs of greater than Grade 3 were considered relevant to determining DLTs. DLTs included absolute lymphocyte count (ALC) Grade 3 and 4 (if ALC does not resolve to baseline grade according to Common Terminology Criteria for Adverse Events (CTCAE) v4 within 5 days post the final injection per cycle of DI-Leu16-IL2), and absolute neutrophil count (ANC) Grade 3 (If ANC does not resolve to at least Grade 2 within 5 days post the final injection per cycle of DI-Leu16-IL2) and Grade 4 (any).
Time frame: First 2 cycles of treatment (each cycle = 21 days)
Population: Safety population included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DI-Leu16-IL2 | Maximum Tolerated Dose (MTD) of DI-Leu16-IL2 | 4.0 mg/m^2 |
Primary
Number of Participants With a DLT
All non-hematologic AEs and all hematologic AEs of greater than Grade 3 were considered relevant to determining DLTs. DLTs included ALC Grade 3 and 4 (if ALC does not resolve to baseline grade according to CTCAE v4 within 5 days post the final injection per cycle of DI-Leu16-IL2), and ANC Grade 3 (If ANC does not resolve to at least Grade 2 within 5 days post the final injection per cycle of DI-Leu16-IL2) and Grade 4 (any).
Time frame: First 2 cycles of treatment (each cycle = 21 days)
Population: Safety population included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DI-Leu16-IL2 | Number of Participants With a DLT | 0 Participants |
| DI-Leu16-IL2 1.0 mg/m^2 | Number of Participants With a DLT | 0 Participants |
| DI-Leu16-IL2 2.0 mg/m^2 | Number of Participants With a DLT | 0 Participants |
| DI-Leu16-IL2 4.0 mg/m^2 | Number of Participants With a DLT | 0 Participants |
| DI-Leu16-IL2 6.0 mg/m^2 | Number of Participants With a DLT | 2 Participants |
Primary
Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria
BOR included complete response (CR), unconfirmed CR (CRu), partial response (PR), stable disease (SD), and progressive disease (PD). CR: 1) Disappearance of all detectable clinical and radiological evidence of disease; 2) lymph nodes (LN) regressed to normal size; 3) other organs (spleen, liver, kidneys) that were enlarged before therapy must have decreased in size; 4) clear bone marrow (BM) infiltrate. CRu: must meet CR criteria 1 and 3, as well as ≥1 of following: residual LN mass \>1.5 cm in greatest transverse diameter; individual nodes that were previously confluent regressed by \>75% in sum of product diameters (SPD); or indeterminate BM. PR: 6 largest dominant nodes or nodal masses decreased by ≤50% in SPD; no increase in size of other nodes; liver or spleen; splenic and hepatic nodules regressed ≥50% in SPD; and no new disease. SD: less than a PR but not PD. PD: 50% increase from nadir in SPD of any abnormal node for PR or nonresponders and appearance of any new lesion.
Time frame: First dose of study drug until first appearance of CR, CRu, PR, SD, or PD (up to 6 months)
Population: Safety population included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DI-Leu16-IL2 | Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | SD | 2 Participants |
| DI-Leu16-IL2 | Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | CR | 0 Participants |
| DI-Leu16-IL2 | Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | PD | 1 Participants |
| DI-Leu16-IL2 | Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | CRu | 0 Participants |
| DI-Leu16-IL2 | Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | PR | 0 Participants |
| DI-Leu16-IL2 1.0 mg/m^2 | Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | SD | 2 Participants |
| DI-Leu16-IL2 1.0 mg/m^2 | Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | PR | 1 Participants |
| DI-Leu16-IL2 1.0 mg/m^2 | Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | CRu | 0 Participants |
| DI-Leu16-IL2 1.0 mg/m^2 | Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | PD | 0 Participants |
| DI-Leu16-IL2 1.0 mg/m^2 | Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | CR | 0 Participants |
| DI-Leu16-IL2 2.0 mg/m^2 | Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | PR | 1 Participants |
| DI-Leu16-IL2 2.0 mg/m^2 | Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | CR | 2 Participants |
| DI-Leu16-IL2 2.0 mg/m^2 | Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | CRu | 0 Participants |
| DI-Leu16-IL2 2.0 mg/m^2 | Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | SD | 1 Participants |
| DI-Leu16-IL2 2.0 mg/m^2 | Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | PD | 4 Participants |
| DI-Leu16-IL2 4.0 mg/m^2 | Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | PD | 4 Participants |
| DI-Leu16-IL2 4.0 mg/m^2 | Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | CR | 1 Participants |
| DI-Leu16-IL2 4.0 mg/m^2 | Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | SD | 2 Participants |
| DI-Leu16-IL2 4.0 mg/m^2 | Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | PR | 0 Participants |
| DI-Leu16-IL2 4.0 mg/m^2 | Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | CRu | 0 Participants |
| DI-Leu16-IL2 6.0 mg/m^2 | Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | PR | 0 Participants |
| DI-Leu16-IL2 6.0 mg/m^2 | Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | SD | 0 Participants |
| DI-Leu16-IL2 6.0 mg/m^2 | Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | CR | 0 Participants |
| DI-Leu16-IL2 6.0 mg/m^2 | Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | PD | 2 Participants |
| DI-Leu16-IL2 6.0 mg/m^2 | Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | CRu | 0 Participants |
Primary
Tumor Measurement: Percent Change From Baseline in Sum of Longest Diameters at the End of Study
Sum of longest diameters is the sum of the longest measured length of each tumor lesion. Baseline value is the last non-missing measurement prior to receiving study drug injection. None of the participants were considered evaluable in 'DI-Leu16-IL2 0.5 mg/m\^2' arm for this outcome measure at the end of study, and therefore, data were not collected for that arm.
Time frame: Baseline, EOS (up to approximately 3 years)
Population: Safety population included all enrolled participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DI-Leu16-IL2 1.0 mg/m^2 | Tumor Measurement: Percent Change From Baseline in Sum of Longest Diameters at the End of Study | -30.657 percent change | Standard Deviation 60.3132 |
| DI-Leu16-IL2 2.0 mg/m^2 | Tumor Measurement: Percent Change From Baseline in Sum of Longest Diameters at the End of Study | -27.412 percent change | Standard Deviation 49.2553 |
| DI-Leu16-IL2 4.0 mg/m^2 | Tumor Measurement: Percent Change From Baseline in Sum of Longest Diameters at the End of Study | 1.398 percent change | Standard Deviation 43.4731 |
| DI-Leu16-IL2 6.0 mg/m^2 | Tumor Measurement: Percent Change From Baseline in Sum of Longest Diameters at the End of Study | 28.516 percent change | Standard Deviation 22.5263 |
Primary
Tumor Measurement: Percent Change From Baseline in Sum of Product of Diameters at the End of Study
Sum of product diameters sums the product of the 2 tumor measurements on each lesion. If only 1 measurement was available, it was used as the longest length and the product of the lengths in the sum. Baseline value is the last non-missing measurement prior to receiving study drug injection. None of the participants were considered evaluable in 'DI-Leu16-IL2 0.5 mg/m\^2' arm for this outcome measure at the end of study, and therefore, data were not collected for that arm.
Time frame: Baseline, end of study (EOS) (up to approximately 3 years)
Population: Safety population included all enrolled participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DI-Leu16-IL2 1.0 mg/m^2 | Tumor Measurement: Percent Change From Baseline in Sum of Product of Diameters at the End of Study | -31.54881 percent change | Standard Deviation 60.445273 |
| DI-Leu16-IL2 2.0 mg/m^2 | Tumor Measurement: Percent Change From Baseline in Sum of Product of Diameters at the End of Study | -26.37248 percent change | Standard Deviation 78.719865 |
| DI-Leu16-IL2 4.0 mg/m^2 | Tumor Measurement: Percent Change From Baseline in Sum of Product of Diameters at the End of Study | 48.83017 percent change | Standard Deviation 120.29112 |
| DI-Leu16-IL2 6.0 mg/m^2 | Tumor Measurement: Percent Change From Baseline in Sum of Product of Diameters at the End of Study | 87.98408 percent change | Standard Deviation 78.864919 |
Secondary
Number of Participants With Anti-DI-Leu16-IL2 Antibodies
Time frame: First dose of study drug up to EOS (up to approximately 3 years)
Population: Due to early termination of study, data for this outcome measure were not collected.