A Study of De-immunized DI-Leu16-IL2 Administered Subcutaneously in Participants With B-cell NHL
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: DI-Leu16-IL2 0.5 mg/m^2 Participants will receive DI-Leu16-IL2 0.5 mg/m^2 subcutaneously (SC) for 3 consecutive days every 3 weeks (21-day cycle) for a total of 4 cycles. |
Drug: DI-Leu16-IL2
DI-Leu16-IL2 will be administered per dose and schedule specified in the arm.
|
| Experimental: DI-Leu16-IL2 1.0 mg/m^2 Participants will receive 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. |
Drug: DI-Leu16-IL2
DI-Leu16-IL2 will be administered per dose and schedule specified in the arm.
|
| Experimental: DI-Leu16-IL2 2.0 mg/m^2 Participants will receive 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. |
Drug: DI-Leu16-IL2
DI-Leu16-IL2 will be administered per dose and schedule specified in the arm.
|
| Experimental: DI-Leu16-IL2 4.0 mg/m^2 Participants will receive 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 |
Drug: DI-Leu16-IL2
DI-Leu16-IL2 will be administered per dose and schedule specified in the arm.
|
| Experimental: DI-Leu16-IL2 6.0 mg/m^2 Participants will receive 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. |
Drug: DI-Leu16-IL2
DI-Leu16-IL2 will be administered per dose and schedule specified in the arm.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- Number of Participants With Anti-DI-Leu16-IL2 Antibodies [First dose of study drug up to EOS (up to approximately 3 years)]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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.
-
Participants must have received prior rituximab-containing therapy.
-
Evaluable disease. In the absence of lymphadenopathy, splenomegaly with defects or measurable extra-medullary disease is acceptable.
-
Participants who have received a prior autologous stem cell transplant are eligible if the transplant occurred >6 months ago.
-
Participants who have received a prior allogeneic stem cell transplant are eligible if:
-
The transplant occurred >6 months ago
-
There is no evidence of active graft versus host disease
-
Systemic immunosuppressive agents (including corticosteroids) have not been received for at least 8 weeks
-
Karnofsky performance scale ≥70%
-
Life expectancy ≥12 weeks
-
Adequate baseline functions:
-
Serum creatinine ≤1.5 mg/deciliter (dL)
-
Total white blood cell (WBC) count ≥3000/microliter (µL) or absolute neutrophil count (ANC) ≥1000/µL
-
Absolute lymphocyte count ≥0.75 * 10^3/µL
-
Platelet count ≥75,000/µL
-
Hematocrit ≥25% or hemoglobin ≥9 grams/100 milliliters (mL)
-
Alanine aminotransferase (ALT) <2.5 * upper limit of normal (ULN)
-
Aspartate aminotransferase (AST) <2.5 * ULN
-
Total bilirubin (TBili) <1.5 * ULN
-
Sodium, potassium, and phosphorus levels no worse than grade 1
-
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.
-
Electrocardiogram (12-lead ECG) QTc ≤480 millisecond (ms)
-
Cardiac stress test (for example, stress thallium scan, stress echocardiography) with normal results if participant is suspected to have coronary artery disease.
-
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).
-
Provide written informed consent prior to any screening procedures
Exclusion Criteria:
-
Evidence of central nervous system lymphoma or lymphomatous meningitis
-
Prior treatment with interleukin 2 (IL2) within the last 5 years
-
Type I hypersensitivity or anaphylactic reactions to murine proteins or to previous infusion of rituximab
-
Pregnant or lactating female
-
An immediate need for palliative radiotherapy or systemic corticosteroid therapy
-
Known intercurrent infections (including hepatitis C virus and human immunodeficiency virus or other conditions), or clinical evidence of these conditions
-
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.
-
Other significant active infection.
-
Major surgery, chemotherapy, investigational agent, or radiation within 30 days of Day 1
-
Uncontrolled hypertension (diastolic greater to or equal to 100 millimeters of mercury [mmHg]) or hypotension (systolic less than or equal to 90 mmHg)
-
History of repeated and clinically relevant episodes of syncope or other paroxysmal, ventricular, or other significant arrhythmias
-
History of medically significant ascites requiring repetitive paracentesis
-
Previous diagnosis of autoimmune disease (Exceptions: participants with autoimmune thyroiditis or vitiligo may be enrolled)
-
Organ transplant recipient
-
History of prior therapy or a serious, uncontrolled medical disorder that in the Investigator's opinion would impair participation in the study
-
Known hypersensitivity to Tween-80 or human immunoglobulin
-
Legal incapacity or limited legal capacity
-
Participants with bulky lymph nodes (LNs) (≥10 centimeters [cm]) or marked splenomegaly (that is, extending into pelvis or crossing the midline).
-
Circulating levels of rituximab >75.0 micrograms (µg)/mL
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | City of Hope | Duarte | California | United States | 91010 |
| 2 | St. Jude Hospital Yorba Linda | Fullerton | California | United States | 92835 |
| 3 | University of Minnesota | Minneapolis | Minnesota | United States | 55455 |
| 4 | Dartmouth-Hitchcock Medical Center | Lebanon | New Hampshire | United States | 03756 |
| 5 | Joe Arlington Cancer Research and Treatment Center | Lubbock | Texas | United States | 97410 |
Sponsors and Collaborators
- Alopexx Oncology, LLC
Investigators
- Study Director: Daniel Vlock, MD, Alopexx Oncology, LLC
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- King DM, Albertini MR, Schalch H, Hank JA, Gan J, Surfus J, Mahvi D, Schiller JH, Warner T, Kim K, Eickhoff J, Kendra K, Reisfeld R, Gillies SD, Sondel P. Phase I clinical trial of the immunocytokine EMD 273063 in melanoma patients. J Clin Oncol. 2004 Nov 15;22(22):4463-73. Epub 2004 Oct 13.
- Ko YJ, Bubley GJ, Weber R, Redfern C, Gold DP, Finke L, Kovar A, Dahl T, Gillies SD. Safety, pharmacokinetics, and biological pharmacodynamics of the immunocytokine EMD 273066 (huKS-IL2): results of a phase I trial in patients with prostate cancer. J Immunother. 2004 May-Jun;27(3):232-9.
- Maloney DG, Liles TM, Czerwinski DK, Waldichuk C, Rosenberg J, Grillo-Lopez A, Levy R. Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma. Blood. 1994 Oct 15;84(8):2457-66.
- AO-101
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | DI-Leu16-IL2 0.5 mg/m^2 | 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 6.0 mg/m^2 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received DI-Leu16-IL2 0.5 milligrams per square meter (mg/m^2) subcutaneously (SC) for 3 consecutive days every 3 weeks (21-day cycle) for a total of 4 cycles. | 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. | 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. | 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. | 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. |
| Period Title: Overall Study | |||||
| STARTED | 3 | 3 | 9 | 7 | 2 |
| Received at Least 1 Dose of Study Drug | 3 | 3 | 9 | 7 | 2 |
| COMPLETED | 0 | 3 | 4 | 0 | 0 |
| NOT COMPLETED | 3 | 0 | 5 | 7 | 2 |
Baseline Characteristics
| Arm/Group Title | DI-Leu16-IL2 0.5 mg/m^2 | 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 6.0 mg/m^2 | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | Total of all reporting groups |
| Overall Participants | 3 | 3 | 9 | 7 | 2 | 24 |
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
51.3
(12.22)
|
66.7
(14.84)
|
64.0
(11.55)
|
59.6
(9.61)
|
57.5
(13.44)
|
60.9
(11.49)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
1
33.3%
|
1
33.3%
|
6
66.7%
|
0
0%
|
2
100%
|
10
41.7%
|
| Male |
2
66.7%
|
2
66.7%
|
3
33.3%
|
7
100%
|
0
0%
|
14
58.3%
|
| Tumor Measurement: Sum of Product of Diameters (centimeters (cm)) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [centimeters (cm)] |
15.11667
(9.726296)
|
12.21667
(12.110806)
|
17.63953
(16.388997)
|
27.95857
(22.005858)
|
27.86500
(10.896515)
|
20.50816
(16.836733)
|
| Tumor Measurement: Sum of Longest of Diameters (cm) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [cm] |
6.000
(3.0414)
|
6.133
(4.3524)
|
9.462
(5.4068)
|
11.100
(5.1901)
|
10.300
(5.6569)
|
9.161
(4.9829)
|
Outcome Measures
| Title | Maximum Tolerated Dose (MTD) of DI-Leu16-IL2 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all enrolled participants who received at least 1 dose of study drug. |
| Arm/Group Title | DI-Leu16-IL2 |
|---|---|
| Arm/Group Description | Participants received assigned doses of DI-Leu16-IL2 SC for 3 consecutive days every 3 weeks (21-day cycle) for a total of 4 cycles. |
| Measure Participants | 24 |
| Number [mg/m^2] |
4.0
|
| Title | Number of Participants With a DLT |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all enrolled participants who received at least 1 dose of study drug. |
| Arm/Group Title | DI-Leu16-IL2 0.5 mg/m^2 | 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 6.0 mg/m^2 |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 3 | 3 | 9 | 7 | 2 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
100%
|
| Title | Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all enrolled participants who received at least 1 dose of study drug. |
| Arm/Group Title | DI-Leu16-IL2 0.5 mg/m^2 | 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 6.0 mg/m^2 |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 3 | 3 | 9 | 7 | 2 |
| CR |
0
0%
|
0
0%
|
2
22.2%
|
1
14.3%
|
0
0%
|
| CRu |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| PR |
0
0%
|
1
33.3%
|
1
11.1%
|
0
0%
|
0
0%
|
| SD |
2
66.7%
|
2
66.7%
|
1
11.1%
|
2
28.6%
|
0
0%
|
| PD |
1
33.3%
|
0
0%
|
4
44.4%
|
4
57.1%
|
2
100%
|
| Title | Tumor Measurement: Percent Change From Baseline in Sum of Product of Diameters at the End of Study |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | DI-Leu16-IL2 0.5 mg/m^2 | 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 6.0 mg/m^2 |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 0 | 3 | 5 | 5 | 2 |
| Mean (Standard Deviation) [percent change] |
-31.54881
(60.445273)
|
-26.37248
(78.719865)
|
48.83017
(120.291120)
|
87.98408
(78.864919)
|
| Title | Tumor Measurement: Percent Change From Baseline in Sum of Longest Diameters at the End of Study |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | DI-Leu16-IL2 0.5 mg/m^2 | 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 6.0 mg/m^2 |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 0 | 3 | 5 | 5 | 2 |
| Mean (Standard Deviation) [percent change] |
-30.657
(60.3132)
|
-27.412
(49.2553)
|
1.398
(43.4731)
|
28.516
(22.5263)
|
| Title | Number of Participants With Anti-DI-Leu16-IL2 Antibodies |
|---|---|
| Description | |
| Time Frame | First dose of study drug up to EOS (up to approximately 3 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to early termination of study, data for this outcome measure were not collected. |
| Arm/Group Title | DI-Leu16-IL2 0.5 mg/m^2 | 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 6.0 mg/m^2 |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 |
Adverse Events
| Time Frame | First dose of study drug up to EOS (up to approximately 3 years) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Safety population included all enrolled participants who received at least 1 dose of study drug. | |||||||||
| Arm/Group Title | DI-Leu16-IL2 0.5 mg/m^2 | 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 6.0 mg/m^2 | |||||
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | |||||
All Cause Mortality |
||||||||||
| DI-Leu16-IL2 0.5 mg/m^2 | 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 6.0 mg/m^2 | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
Serious Adverse Events |
||||||||||
| DI-Leu16-IL2 0.5 mg/m^2 | 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 6.0 mg/m^2 | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 2/3 (66.7%) | 1/9 (11.1%) | 3/7 (42.9%) | 1/2 (50%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Thrombocytopenia | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Melaena | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| General disorders | ||||||||||
| Pyrexia | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/7 (28.6%) | 0/2 (0%) | |||||
| Immune system disorders | ||||||||||
| Cytokine release syndrome | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/7 (0%) | 1/2 (50%) | |||||
| Infections and infestations | ||||||||||
| Abdominal infection | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Renal and urinary disorders | ||||||||||
| Renal failure acute | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Dyspnoea | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| DI-Leu16-IL2 0.5 mg/m^2 | 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 6.0 mg/m^2 | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 3/3 (100%) | 9/9 (100%) | 7/7 (100%) | 2/2 (100%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 0/3 (0%) | 2/3 (66.7%) | 6/9 (66.7%) | 5/7 (71.4%) | 1/2 (50%) | |||||
| Thrombocytopenia | 0/3 (0%) | 1/3 (33.3%) | 3/9 (33.3%) | 1/7 (14.3%) | 2/2 (100%) | |||||
| Neutropenia | 0/3 (0%) | 1/3 (33.3%) | 1/9 (11.1%) | 2/7 (28.6%) | 0/2 (0%) | |||||
| Eosinophilia | 1/3 (33.3%) | 2/3 (66.7%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Febrile neutropenia | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Cardiac disorders | ||||||||||
| Tachycardia | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 2/7 (28.6%) | 2/2 (100%) | |||||
| Sinus bradycardia | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Palpitations | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Sinus tachycardia | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Ear and labyrinth disorders | ||||||||||
| Cerumen impaction | 0/3 (0%) | 1/3 (33.3%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Hypoacusis | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Eye disorders | ||||||||||
| Diplopia | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Dry eye | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Eyelid oedema | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Diarrhoea | 2/3 (66.7%) | 1/3 (33.3%) | 5/9 (55.6%) | 2/7 (28.6%) | 0/2 (0%) | |||||
| Nausea | 1/3 (33.3%) | 0/3 (0%) | 4/9 (44.4%) | 3/7 (42.9%) | 1/2 (50%) | |||||
| Vomiting | 1/3 (33.3%) | 0/3 (0%) | 2/9 (22.2%) | 3/7 (42.9%) | 1/2 (50%) | |||||
| Abdominal pain | 1/3 (33.3%) | 1/3 (33.3%) | 3/9 (33.3%) | 0/7 (0%) | 0/2 (0%) | |||||
| Constipation | 1/3 (33.3%) | 0/3 (0%) | 2/9 (22.2%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Dyspepsia | 2/3 (66.7%) | 1/3 (33.3%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Abdominal distension | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/7 (14.3%) | 1/2 (50%) | |||||
| Abdominal pain upper | 1/3 (33.3%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Dry mouth | 0/3 (0%) | 1/3 (33.3%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Lip pain | 0/3 (0%) | 1/3 (33.3%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Oral Pain | 0/3 (0%) | 2/3 (66.7%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Colitis | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/7 (0%) | 1/2 (50%) | |||||
| Dysphagia | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Epigastric discomfort | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Faeces discoloured | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Flatulence | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Gastritis | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Gingival pain | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Glossodynia | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Lip swelling | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Rectal haemorrhage | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Stomatitis | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Tongue disorder | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Toothache | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| General disorders | ||||||||||
| Injection site erythema | 2/3 (66.7%) | 3/3 (100%) | 7/9 (77.8%) | 6/7 (85.7%) | 2/2 (100%) | |||||
| Injection site pruritus | 3/3 (100%) | 3/3 (100%) | 6/9 (66.7%) | 4/7 (57.1%) | 1/2 (50%) | |||||
| Chills | 1/3 (33.3%) | 1/3 (33.3%) | 5/9 (55.6%) | 7/7 (100%) | 2/2 (100%) | |||||
| Fatigue | 1/3 (33.3%) | 3/3 (100%) | 4/9 (44.4%) | 6/7 (85.7%) | 1/2 (50%) | |||||
| Pyrexia | 1/3 (33.3%) | 1/3 (33.3%) | 5/9 (55.6%) | 3/7 (42.9%) | 2/2 (100%) | |||||
| Injection site induration | 1/3 (33.3%) | 2/3 (66.7%) | 4/9 (44.4%) | 3/7 (42.9%) | 0/2 (0%) | |||||
| Injection site rash | 1/3 (33.3%) | 1/3 (33.3%) | 3/9 (33.3%) | 4/7 (57.1%) | 1/2 (50%) | |||||
| Pain | 0/3 (0%) | 3/3 (100%) | 2/9 (22.2%) | 3/7 (42.9%) | 1/2 (50%) | |||||
| Injection site pain | 1/3 (33.3%) | 2/3 (66.7%) | 2/9 (22.2%) | 1/7 (14.3%) | 1/2 (50%) | |||||
| Oedema peripheral | 0/3 (0%) | 2/3 (66.7%) | 2/9 (22.2%) | 1/7 (14.3%) | 1/2 (50%) | |||||
| Injection site oedema | 0/3 (0%) | 1/3 (33.3%) | 3/9 (33.3%) | 0/7 (0%) | 1/2 (50%) | |||||
| Influenza like illness | 0/3 (0%) | 0/3 (0%) | 2/9 (22.2%) | 2/7 (28.6%) | 0/2 (0%) | |||||
| Injection site swelling | 1/3 (33.3%) | 1/3 (33.3%) | 1/9 (11.1%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Injection site discolouration | 0/3 (0%) | 0/3 (0%) | 3/9 (33.3%) | 0/7 (0%) | 0/2 (0%) | |||||
| Injection site inflammation | 1/3 (33.3%) | 0/3 (0%) | 2/9 (22.2%) | 0/7 (0%) | 0/2 (0%) | |||||
| Injection site warmth | 1/3 (33.3%) | 2/3 (66.7%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Local swelling | 0/3 (0%) | 0/3 (0%) | 2/9 (22.2%) | 0/7 (0%) | 0/2 (0%) | |||||
| Asthenia | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Face oedema | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/7 (0%) | 1/2 (50%) | |||||
| Feeling cold | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Generalised oedema | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Infusion site haematoma | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Injection site anaesthesia | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Injection site discomfort | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Injection site dryness | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Injection site haemorrhage | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Injection site mass | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Injection site nodule | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Injection site vesicles | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Oedema | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Thirst | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Immune system disorders | ||||||||||
| Cytokine release syndrome | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Hypogammaglobulinaemia | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Allergy to arthropod bite | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Hypersensitivity | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Infections and infestations | ||||||||||
| Upper respiratory tract infection | 0/3 (0%) | 1/3 (33.3%) | 1/9 (11.1%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Cellulitis | 1/3 (33.3%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Rhinitis | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Influenza | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Nasopharyngitis | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Oral Candidiasis | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Otitis media acute | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Respiratory syncytial virus infection | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Sinusitis | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Urinary tract infection | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Fall | 0/3 (0%) | 2/3 (66.7%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Incision site pruritus | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Ligament injury | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Investigations | ||||||||||
| Lymphocyte count decreased | 0/3 (0%) | 0/3 (0%) | 4/9 (44.4%) | 2/7 (28.6%) | 1/2 (50%) | |||||
| Alanine aminotransferase increased | 0/3 (0%) | 0/3 (0%) | 2/9 (22.2%) | 1/7 (14.3%) | 2/2 (100%) | |||||
| Blood alkaline phosphatase increased | 0/3 (0%) | 0/3 (0%) | 2/9 (22.2%) | 1/7 (14.3%) | 2/2 (100%) | |||||
| Platelet count decreased | 0/3 (0%) | 0/3 (0%) | 3/9 (33.3%) | 2/7 (28.6%) | 0/2 (0%) | |||||
| Blood creatinine increased | 0/3 (0%) | 1/3 (33.3%) | 1/9 (11.1%) | 2/7 (28.6%) | 0/2 (0%) | |||||
| Electrocardiogram QT prolonged | 0/3 (0%) | 0/3 (0%) | 2/9 (22.2%) | 2/7 (28.6%) | 0/2 (0%) | |||||
| Aspartate aminotransferase increased | 0/3 (0%) | 0/3 (0%) | 2/9 (22.2%) | 0/7 (0%) | 1/2 (50%) | |||||
| Weight increased | 0/3 (0%) | 1/3 (33.3%) | 2/9 (22.2%) | 0/7 (0%) | 0/2 (0%) | |||||
| White blood cell count decreased | 0/3 (0%) | 0/3 (0%) | 2/9 (22.2%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Eosinophil count increased | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/7 (28.6%) | 0/2 (0%) | |||||
| Neutrophil count decreased | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Weight decreased | 0/3 (0%) | 1/3 (33.3%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Blood bilirubin increased | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Blood creatine phosphokinase increased | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Blood glucose increased | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Blood lactate dehydrogenase increased | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Blood potassium increased | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Blood urea increased | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Cardiac murmur | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/7 (0%) | 1/2 (50%) | |||||
| Electrocardiogram QT interval | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| General physical condition abnormal | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Glomerular filtration rate decreased | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Haematocrit decreased | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Haemoglobin decreased | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| International normalised ratio increased | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Mean cell haemoglobin decreased | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Neutrophil count increased | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Protein total increased | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Decreased appetite | 0/3 (0%) | 1/3 (33.3%) | 5/9 (55.6%) | 3/7 (42.9%) | 1/2 (50%) | |||||
| Hypoalbuminaemia | 0/3 (0%) | 0/3 (0%) | 2/9 (22.2%) | 2/7 (28.6%) | 1/2 (50%) | |||||
| Hypocalcaemia | 0/3 (0%) | 1/3 (33.3%) | 2/9 (22.2%) | 1/7 (14.3%) | 1/2 (50%) | |||||
| Hyperglycaemia | 0/3 (0%) | 1/3 (33.3%) | 1/9 (11.1%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Hypomagnesaemia | 1/3 (33.3%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 1/2 (50%) | |||||
| Hyperkalaemia | 0/3 (0%) | 2/3 (66.7%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Hypokalaemia | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 1/2 (50%) | |||||
| Hyponatraemia | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Hypophosphataemia | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/7 (14.3%) | 1/2 (50%) | |||||
| Central obesity | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Dehydration | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Hypernatraemia | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Hypoglycaemia | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Tumour lysis syndrome | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Back pain | 0/3 (0%) | 1/3 (33.3%) | 1/9 (11.1%) | 2/7 (28.6%) | 1/2 (50%) | |||||
| Arthralgia | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 2/7 (28.6%) | 0/2 (0%) | |||||
| Muscle spasms | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Muscular weakness | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/7 (28.6%) | 0/2 (0%) | |||||
| Musculoskeletal pain | 0/3 (0%) | 0/3 (0%) | 2/9 (22.2%) | 0/7 (0%) | 0/2 (0%) | |||||
| Myalgia | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Bone pain | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Groin pain | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Pain in extremity | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Pain in jaw | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Acoustic neuroma | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Lymphoma | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Non-hodgkin's lymphoma | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Nervous system disorders | ||||||||||
| Dizziness | 1/3 (33.3%) | 2/3 (66.7%) | 1/9 (11.1%) | 1/7 (14.3%) | 1/2 (50%) | |||||
| Headache | 0/3 (0%) | 1/3 (33.3%) | 2/9 (22.2%) | 2/7 (28.6%) | 0/2 (0%) | |||||
| Dysgeusia | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 2/7 (28.6%) | 0/2 (0%) | |||||
| Neuropathy peripheral | 0/3 (0%) | 0/3 (0%) | 2/9 (22.2%) | 0/7 (0%) | 0/2 (0%) | |||||
| Ataxia | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Hypoaesthesia | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Memory impairment | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Neurotoxicity | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Nystagmus | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Peripheral sensory neuropathy | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Somnolence | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Psychiatric disorders | ||||||||||
| Insomnia | 0/3 (0%) | 1/3 (33.3%) | 4/9 (44.4%) | 1/7 (14.3%) | 1/2 (50%) | |||||
| Anxiety | 1/3 (33.3%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Depression | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Depressed mood | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Sleep disorder due to general medical condition, insomnia Type | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Renal and urinary disorders | ||||||||||
| Chromaturia | 0/3 (0%) | 1/3 (33.3%) | 1/9 (11.1%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Renal failure acute | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Haematuria | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Micturition urgency | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Urine odour abnormal | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Cough | 1/3 (33.3%) | 2/3 (66.7%) | 1/9 (11.1%) | 1/7 (14.3%) | 2/2 (100%) | |||||
| Nasal congestion | 0/3 (0%) | 1/3 (33.3%) | 2/9 (22.2%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Dyspnoea | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 1/2 (50%) | |||||
| Dyspnoea exertional | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 2/7 (28.6%) | 0/2 (0%) | |||||
| Rhinorrhoea | 1/3 (33.3%) | 1/3 (33.3%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Sinus congestion | 0/3 (0%) | 1/3 (33.3%) | 1/9 (11.1%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Oropharyngeal pain | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/7 (28.6%) | 0/2 (0%) | |||||
| Dry throat | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Dysphonia | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Pleural effusion | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/7 (0%) | 1/2 (50%) | |||||
| Productive cough | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Rales | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Upper respiratory tract congestion | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Night sweats | 0/3 (0%) | 0/3 (0%) | 2/9 (22.2%) | 2/7 (28.6%) | 1/2 (50%) | |||||
| Pruritus | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 2/7 (28.6%) | 1/2 (50%) | |||||
| Rash | 0/3 (0%) | 0/3 (0%) | 2/9 (22.2%) | 2/7 (28.6%) | 0/2 (0%) | |||||
| Dry skin | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 2/7 (28.6%) | 0/2 (0%) | |||||
| Hyperhidrosis | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 2/7 (28.6%) | 0/2 (0%) | |||||
| Rash macular | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Skin hyperpigmentation | 1/3 (33.3%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Cold sweat | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Decubitus ulcer | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Dermatitis contact | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Drug eruption | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Erythema | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Exfoliative rash | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Pruritus allergic | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Pruritus generalised | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Rash erythematous | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Rash maculo-papular | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Rash morbilliform | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Skin hypertrophy | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Surgical and medical procedures | ||||||||||
| Sinus operation | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/7 (0%) | 0/2 (0%) | |||||
| Vascular disorders | ||||||||||
| Hypotension | 0/3 (0%) | 1/3 (33.3%) | 2/9 (22.2%) | 1/7 (14.3%) | 1/2 (50%) | |||||
| Flushing | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 1/7 (14.3%) | 0/2 (0%) | |||||
| Hypertension | 1/3 (33.3%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
| Capillary leak syndrome | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/7 (0%) | 1/2 (50%) | |||||
| Deep vein thrombosis | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/7 (0%) | 0/2 (0%) | |||||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Alopexx Oncology, LLC |
| Phone | |
| daniel.vlock@alopexx.com |
- AO-101