Trial Outcomes & Findings for Open-Label Extension Study of De-immunized DI-Leu16-IL2 Immunocytokine Administered in Participants With B-cell NHL (NCT NCT02151903)

NCT ID: NCT02151903

Last Updated: 2020-11-27

Results Overview

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 centimeters (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.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

5 participants

Primary outcome timeframe

First dose of study drug until first appearance of CR, CRu, PR, SD, or PD (up to 20 months)

Results posted on

2020-11-27

Participant Flow

Participants who, in the opinion of the Investigator, exhibited a beneficial effect without a dose-limiting toxicity (DLT) in the dose-escalation Study AO-101 (NCT01874288) (Main Study) were allowed to continue treatment with DI-Leu16-IL2 in this open-label extension study.

Participant milestones

Participant milestones
Measure	DI-Leu16-IL2 1.0 mg/m^2 Participants received DI-Leu16-IL2 1.0 milligrams per square meter (mg/m\^2) subcutaneously (SC) for 3 consecutive days every 3 weeks (21-day cycle). Participants continued to receive therapy through the duration of the study as long as they were having clinical benefit and not experiencing any untoward side effects.	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). Participants continued to receive therapy through the duration of the study as long as they were having clinical benefit and not experiencing any untoward side effects.
Overall Study STARTED	3	2
Overall Study Received at Least 1 Dose of Study Drug	3	2
Overall Study COMPLETED	0	1
Overall Study NOT COMPLETED	3	1

Reasons for withdrawal

Reasons for withdrawal
Measure	DI-Leu16-IL2 1.0 mg/m^2 Participants received DI-Leu16-IL2 1.0 milligrams per square meter (mg/m\^2) subcutaneously (SC) for 3 consecutive days every 3 weeks (21-day cycle). Participants continued to receive therapy through the duration of the study as long as they were having clinical benefit and not experiencing any untoward side effects.	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). Participants continued to receive therapy through the duration of the study as long as they were having clinical benefit and not experiencing any untoward side effects.
Overall Study Withdrawal by Subject	1	0
Overall Study Progressive disease	2	1

Baseline Characteristics

Open-Label Extension Study of De-immunized DI-Leu16-IL2 Immunocytokine Administered in Participants With B-cell NHL

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	DI-Leu16-IL2 1.0 mg/m^2 n=3 Participants Participants received DI-Leu16-IL2 1.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle). Participants continued to receive therapy through the duration of the study as long as they were having clinical benefit and not experiencing any untoward side effects.	DI-Leu16-IL2 2.0 mg/m^2 n=2 Participants Participants received DI-Leu16-IL2 2.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle). Participants continued to receive therapy through the duration of the study as long as they were having clinical benefit and not experiencing any untoward side effects.	Total n=5 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: First dose of study drug until first appearance of CR, CRu, PR, SD, or PD (up to 20 months)

Population: Safety population included all enrolled participants who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	DI-Leu16-IL2 1.0 mg/m^2 n=3 Participants Participants received DI-Leu16-IL2 1.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle). Participants continued to receive therapy through the duration of the study as long as they were having clinical benefit and not experiencing any untoward side effects.	DI-Leu16-IL2 2.0 mg/m^2 n=2 Participants Participants received DI-Leu16-IL2 2.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle). Participants continued to receive therapy through the duration of the study as long as they were having clinical benefit and not experiencing any untoward side effects.
Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria CR	0 Participants	1 Participants
Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria CRu	0 Participants	0 Participants
Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria PR	0 Participants	0 Participants
Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria SD	1 Participants	0 Participants
Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria PD	1 Participants	1 Participants

PRIMARY outcome

Timeframe: Baseline, end of study (EOS) (up to approximately 32 months)

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. None of the participants were considered evaluable in 'DI-Leu16-IL2 2.0 mg/m\^2' arm for this outcome measure at the end of study, and therefore, data were not collected for that arm.

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 in the Main Study AO-101.

Outcome measures

Outcome measures
Measure	DI-Leu16-IL2 1.0 mg/m^2 n=2 Participants Participants received DI-Leu16-IL2 1.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle). Participants continued to receive therapy through the duration of the study as long as they were having clinical benefit and not experiencing any untoward side effects.	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). Participants continued to receive therapy through the duration of the study as long as they were having clinical benefit and not experiencing any untoward side effects.
Tumor Measurement: Percent Change From Baseline in Sum of Product of Diameters at the End of Study	-22.86066 percent change Standard Deviation 9.805965	—

PRIMARY outcome

Timeframe: Baseline, EOS (up to approximately 32 months)

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 in the Main Study AO-101. None of the participants were considered evaluable in 'DI-Leu16-IL2 2.0 mg/m\^2' arm for this outcome measure at the end of study, and therefore, data were not collected for that arm

Outcome measures

Outcome measures
Measure	DI-Leu16-IL2 1.0 mg/m^2 n=2 Participants Participants received DI-Leu16-IL2 1.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle). Participants continued to receive therapy through the duration of the study as long as they were having clinical benefit and not experiencing any untoward side effects.	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). Participants continued to receive therapy through the duration of the study as long as they were having clinical benefit and not experiencing any untoward side effects.
Tumor Measurement: Percent Change From Baseline in Sum of Longest Diameters at the End of Study	-11.638 percent change Standard Deviation 1.5001	—

SECONDARY outcome

Timeframe: First dose of study drug up to EOS (up to 20 months)

Population: Safety population included all enrolled participants who received at least 1 dose of study drug.

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs were defined as AEs with onset at the time of or following the start of treatment with study drug, or AEs starting before the start of treatment but increasing in severity or relationship at the time of or following the start of treatment. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Outcome measures

Outcome measures
Measure	DI-Leu16-IL2 1.0 mg/m^2 n=3 Participants Participants received DI-Leu16-IL2 1.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle). Participants continued to receive therapy through the duration of the study as long as they were having clinical benefit and not experiencing any untoward side effects.	DI-Leu16-IL2 2.0 mg/m^2 n=2 Participants Participants received DI-Leu16-IL2 2.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle). Participants continued to receive therapy through the duration of the study as long as they were having clinical benefit and not experiencing any untoward side effects.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Any TEAEs	3 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAEs	2 Participants	0 Participants

SECONDARY outcome

Timeframe: First dose of study drug up to EOS (up to 20 months)

Population: Safety population included all enrolled participants who received at least 1 dose of study drug.

TEAEs were defined as AEs with onset at the time of or following the start of treatment with study drug, or AEs starting before the start of treatment but increasing in severity or relationship at the time of or following the start of treatment. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Clinically significant hematology and serum chemistry abnormalities were identified at the Investigator's discretion.

Outcome measures

Outcome measures
Measure	DI-Leu16-IL2 1.0 mg/m^2 n=3 Participants Participants received DI-Leu16-IL2 1.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle). Participants continued to receive therapy through the duration of the study as long as they were having clinical benefit and not experiencing any untoward side effects.	DI-Leu16-IL2 2.0 mg/m^2 n=2 Participants Participants received DI-Leu16-IL2 2.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle). Participants continued to receive therapy through the duration of the study as long as they were having clinical benefit and not experiencing any untoward side effects.
Number of Participants With a TEAE That Was Considered Related to a Clinically Significant Hematology or Serum Chemistry Abnormality	3 Participants	0 Participants

SECONDARY outcome

Timeframe: First dose of study drug up to EOS (up to 20 months)

Population: Safety population included all enrolled participants who received at least 1 dose of study drug.

Clinically significant abnormal physical exams included extremities, head, ears, eyes, nose, throat, abdomen, respiratory system, lymphatic system, and integumentary system. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Clinically significant abnormal physical exams were identified at the Investigator's discretion.

Outcome measures

Outcome measures
Measure	DI-Leu16-IL2 1.0 mg/m^2 n=3 Participants Participants received DI-Leu16-IL2 1.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle). Participants continued to receive therapy through the duration of the study as long as they were having clinical benefit and not experiencing any untoward side effects.	DI-Leu16-IL2 2.0 mg/m^2 n=2 Participants Participants received DI-Leu16-IL2 2.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle). Participants continued to receive therapy through the duration of the study as long as they were having clinical benefit and not experiencing any untoward side effects.
Number of Participants With a Clinically Significant Abnormal Physical Exam	3 Participants	1 Participants

Adverse Events

DI-Leu16-IL2 1.0 mg/m^2

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

DI-Leu16-IL2 2.0 mg/m^2

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	DI-Leu16-IL2 1.0 mg/m^2 n=3 participants at risk Participants received DI-Leu16-IL2 1.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle). Participants continued to receive therapy through the duration of the study as long as they were having clinical benefit and not experiencing any untoward side effects.	DI-Leu16-IL2 2.0 mg/m^2 n=2 participants at risk Participants received DI-Leu16-IL2 2.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle). Participants continued to receive therapy through the duration of the study as long as they were having clinical benefit and not experiencing any untoward side effects.
Blood and lymphatic system disorders Anaemia	33.3% 1/3 • First dose of study drug up to EOS (up to 20 months) Safety population included all enrolled participants who received at least 1 dose of study drug.	0.00% 0/2 • First dose of study drug up to EOS (up to 20 months) Safety population included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders Melena	33.3% 1/3 • First dose of study drug up to EOS (up to 20 months) Safety population included all enrolled participants who received at least 1 dose of study drug.	0.00% 0/2 • First dose of study drug up to EOS (up to 20 months) Safety population included all enrolled participants who received at least 1 dose of study drug.

Other adverse events

Additional Information

Chief Medical Officer

Alopexx Oncology, LLC

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60