Trial Outcomes & Findings for Nivolumab (Opdivo®) Plus ABI-009 (Nab-rapamycin) for Advanced Sarcoma and Certain Cancers (NCT NCT03190174)
NCT ID: NCT03190174
Last Updated: 2025-02-17
Results Overview
The maximum tolerated dose is defined as the highest safely tolerated dose, where not more than one patient experienced dose-limiting toxicity (DLT), with the next higher dose level having at least two patients who experienced DLT.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
34 participants
Primary outcome timeframe
Week 6
Results posted on
2025-02-17
Participant Flow
This was an open-label, single-center, dose-finding phase IB study using a fixed dose of nivolumab and escalating doses of nab-sirolimus given intravenously. Patients were enrolled from August 2017 to July 2021 at the Sarcoma Oncology Center, Santa Monica CA 90403. The study was conducted in accordance with the Declaration of Helsinki and approved by the Western Institutional Review Board (Protocol Code 20151429 on September 8, 2017) for studies involving humans.
Participant milestones
| Measure |
Dose Escalation Phase 1 Dose Level I
The study will employ the standard "cohort of three" design. Three patients are treated at each dose level with expansion to six patients per cohort if DLT is observed in one of the three initially enrolled patients at each dose level. If no DLT occurs after 2 doses, escalation to the next dose level will be permitted. The maximum tolerated dose is defined as the highest safely tolerated dose, where not more than one patient experienced DLT, with the next higher dose level having at least two patients who experienced DLT. Patients in the dose escalation study may continue treatment at their designated dose levels up to eighteen 3-week cycles or until significant disease progression or unacceptable toxicity occurs. No intra-patient dose escalation will take place.
|
Dose Escalation Phase 1 Dose Level II
The study will employ the standard "cohort of three" design. Three patients are treated at each dose level with expansion to six patients per cohort if DLT is observed in one of the three initially enrolled patients at each dose level. If no DLT occurs after 2 doses, escalation to the next dose level will be permitted. The maximum tolerated dose is defined as the highest safely tolerated dose, where not more than one patient experienced DLT, with the next higher dose level having at least two patients who experienced DLT. Patients in the dose escalation study may continue treatment at their designated dose levels up to eighteen 3-week cycles or until significant disease progression or unacceptable toxicity occurs. No intra-patient dose escalation will take place.
|
Dose Escalation Phase 1 Dose Level III
The study will employ the standard "cohort of three" design. Three patients are treated at each dose level with expansion to six patients per cohort if DLT is observed in one of the three initially enrolled patients at each dose level. If no DLT occurs after 2 doses, escalation to the next dose level will be permitted. The maximum tolerated dose is defined as the highest safely tolerated dose, where not more than one patient experienced DLT, with the next higher dose level having at least two patients who experienced DLT. Patients in the dose escalation study may continue treatment at their designated dose levels up to eighteen 3-week cycles or until significant disease progression or unacceptable toxicity occurs. No intra-patient dose escalation will take place.
|
Expansion Phase 1b Part
Following dose escalation, an additional 22-28 patients will receive ABI-009 at the MTD and defined doses of nivolumab to assess overall safety and potential efficacy in a greater number of patients. Patients in the expansion phase of the study may continue treatment up to 18 3-week treatment cycles or until significant disease progression or unacceptable toxicity occurs.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
3
|
3
|
25
|
|
Overall Study
COMPLETED
|
3
|
3
|
3
|
25
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Nivolumab (Opdivo®) Plus ABI-009 (Nab-rapamycin) for Advanced Sarcoma and Certain Cancers
Baseline characteristics by cohort
| Measure |
Phase 1: 56 mg/m^2
n=3 Participants
This was an open-label, single-center, dose-finding phase IB study using a fixed dose of nivolumab and escalating doses of nab-sirolimus given intravenously. Patients were enrolled from August 2017 to July 2021. The study was conducted in accordance with the Declaration of Helsinki and approved by the Western Institutional Review Board (Protocol Code 20151429 on September 8, 2017) for studies involving humans.
|
Phase 1: 75mg/m^2
n=3 Participants
This was an open-label, single-center, dose-finding phase IB study using a fixed dose of nivolumab and escalating doses of nab-sirolimus given intravenously. Patients were enrolled from August 2017 to July 2021. The study was conducted in accordance with the Declaration of Helsinki and approved by the Western Institutional Review Board (Protocol Code 20151429 on September 8, 2017) for studies involving humans.
|
Phase 1: 100 mg/m^2
n=3 Participants
This was an open-label, single-center, dose-finding phase IB study using a fixed dose of nivolumab and escalating doses of nab-sirolimus given intravenously. Patients were enrolled from August 2017 to July 2021. The study was conducted in accordance with the Declaration of Helsinki and approved by the Western Institutional Review Board (Protocol Code 20151429 on September 8, 2017) for studies involving humans.
|
Phase 1b: 100 mg/m^2
n=25 Participants
This was an open-label, single-center, dose-finding phase IB study using a fixed dose of nivolumab and escalating doses of nab-sirolimus given intravenously. Patients were enrolled from August 2017 to July 2021. The study was conducted in accordance with the Declaration of Helsinki and approved by the Western Institutional Review Board (Protocol Code 20151429 on September 8, 2017) for studies involving humans.
|
Total
n=34 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
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
25 Participants
n=4 Participants
|
31 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Sex: Female, Male
Sex · Female
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
15 Participants
n=21 Participants
|
|
Sex: Female, Male
Sex · Male
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
19 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
22 Participants
n=4 Participants
|
31 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Week 6Population: Intention-to-treat population (all participant assigned to the Phase I dose escalation part of the study).
The maximum tolerated dose is defined as the highest safely tolerated dose, where not more than one patient experienced dose-limiting toxicity (DLT), with the next higher dose level having at least two patients who experienced DLT.
Outcome measures
| Measure |
Dose Escalation Phase 1
n=9 Participants
The study will employ the standard "cohort of three" design. Patients receive ABI-009 in level I dose - 56 mg/m\^2, in level II dose - 75 mg/m\^2, and level III dose - 100 mg/m\^2, each with defined dose of nivolumab - 240 mg IV 30 min. q 3 weeks.
|
|---|---|
|
Maximum Tolerated Dose of ABI-009
|
100 mg/m^2
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Per pre-specified analysis, only participants in the expansion phase of the study were evaluated.
The disease control rate is the percent of patients with complete response, partial response and stable disease.
Outcome measures
| Measure |
Dose Escalation Phase 1
n=25 Participants
The study will employ the standard "cohort of three" design. Patients receive ABI-009 in level I dose - 56 mg/m\^2, in level II dose - 75 mg/m\^2, and level III dose - 100 mg/m\^2, each with defined dose of nivolumab - 240 mg IV 30 min. q 3 weeks.
|
|---|---|
|
Disease Control Rate
|
22 Participants
|
SECONDARY outcome
Timeframe: 24 weeksPopulation: Per pre-specified analysis, only participants in the expansion phase of the study were evaluated.
Progression free survival is the time from start of treatment to disease progression or death.
Outcome measures
| Measure |
Dose Escalation Phase 1
n=25 Participants
The study will employ the standard "cohort of three" design. Patients receive ABI-009 in level I dose - 56 mg/m\^2, in level II dose - 75 mg/m\^2, and level III dose - 100 mg/m\^2, each with defined dose of nivolumab - 240 mg IV 30 min. q 3 weeks.
|
|---|---|
|
Progression Free Survival
|
22 Participants
|
SECONDARY outcome
Timeframe: 30 weeksPopulation: Per pre-specified analysis, only participants in the expansion phase of the study were evaluated.
The overall survival is the time from treatment initiation to death.
Outcome measures
| Measure |
Dose Escalation Phase 1
n=25 Participants
The study will employ the standard "cohort of three" design. Patients receive ABI-009 in level I dose - 56 mg/m\^2, in level II dose - 75 mg/m\^2, and level III dose - 100 mg/m\^2, each with defined dose of nivolumab - 240 mg IV 30 min. q 3 weeks.
|
|---|---|
|
Overall Survival
|
22 Participants
|
Adverse Events
Dose Escalation Phase 1 Part I
Serious events: 0 serious events
Other events: 0 other events
Deaths: 3 deaths
Dose Escalation Phase 1 Part II
Serious events: 0 serious events
Other events: 0 other events
Deaths: 3 deaths
Dose Escalation Phase 1 Part III
Serious events: 0 serious events
Other events: 0 other events
Deaths: 3 deaths
Expansion Phase 1b
Serious events: 3 serious events
Other events: 2 other events
Deaths: 21 deaths
Serious adverse events
| Measure |
Dose Escalation Phase 1 Part I
n=3 participants at risk
The study will employ the standard "cohort of three" design. Patients receive ABI-009 in level I dose - 56 mg/m\^2 and defined dose of nivolumab - 240 mg IV 30 min. q 3 weeks.
|
Dose Escalation Phase 1 Part II
n=3 participants at risk
The study will employ the standard "cohort of three" design. Patients receive ABI-009 in level II dose - 75 mg/m\^2 and defined dose of nivolumab - 240 mg IV 30 min. q 3 weeks.
|
Dose Escalation Phase 1 Part III
n=3 participants at risk
The study will employ the standard "cohort of three" design. Patients receive ABI-009 in level III dose - 100 mg/m\^2 and defined dose of nivolumab - 240 mg IV 30 min. q 3 weeks.
|
Expansion Phase 1b
n=25 participants at risk
Following dose escalation, an additional 25 patients will receive ABI-009 at the MTD and defined doses of nivolumab to assess overall safety and potential efficacy in a greater number of patients. Patients in the expansion phase of the study may continue treatment up to 18 three-week cycles or until significant disease progression or unacceptable toxicity occurs.
|
|---|---|---|---|---|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/3 • 3.8 years
The definition of adverse event and/or serious adverse event used to collect adverse event information does not differ from that of the clinicaltrials.gov.
|
0.00%
0/3 • 3.8 years
The definition of adverse event and/or serious adverse event used to collect adverse event information does not differ from that of the clinicaltrials.gov.
|
0.00%
0/3 • 3.8 years
The definition of adverse event and/or serious adverse event used to collect adverse event information does not differ from that of the clinicaltrials.gov.
|
4.0%
1/25 • Number of events 1 • 3.8 years
The definition of adverse event and/or serious adverse event used to collect adverse event information does not differ from that of the clinicaltrials.gov.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/3 • 3.8 years
The definition of adverse event and/or serious adverse event used to collect adverse event information does not differ from that of the clinicaltrials.gov.
|
0.00%
0/3 • 3.8 years
The definition of adverse event and/or serious adverse event used to collect adverse event information does not differ from that of the clinicaltrials.gov.
|
0.00%
0/3 • 3.8 years
The definition of adverse event and/or serious adverse event used to collect adverse event information does not differ from that of the clinicaltrials.gov.
|
12.0%
3/25 • Number of events 3 • 3.8 years
The definition of adverse event and/or serious adverse event used to collect adverse event information does not differ from that of the clinicaltrials.gov.
|
Other adverse events
| Measure |
Dose Escalation Phase 1 Part I
n=3 participants at risk
The study will employ the standard "cohort of three" design. Patients receive ABI-009 in level I dose - 56 mg/m\^2 and defined dose of nivolumab - 240 mg IV 30 min. q 3 weeks.
|
Dose Escalation Phase 1 Part II
n=3 participants at risk
The study will employ the standard "cohort of three" design. Patients receive ABI-009 in level II dose - 75 mg/m\^2 and defined dose of nivolumab - 240 mg IV 30 min. q 3 weeks.
|
Dose Escalation Phase 1 Part III
n=3 participants at risk
The study will employ the standard "cohort of three" design. Patients receive ABI-009 in level III dose - 100 mg/m\^2 and defined dose of nivolumab - 240 mg IV 30 min. q 3 weeks.
|
Expansion Phase 1b
n=25 participants at risk
Following dose escalation, an additional 25 patients will receive ABI-009 at the MTD and defined doses of nivolumab to assess overall safety and potential efficacy in a greater number of patients. Patients in the expansion phase of the study may continue treatment up to 18 three-week cycles or until significant disease progression or unacceptable toxicity occurs.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Oral mucositis
|
0.00%
0/3 • 3.8 years
The definition of adverse event and/or serious adverse event used to collect adverse event information does not differ from that of the clinicaltrials.gov.
|
0.00%
0/3 • 3.8 years
The definition of adverse event and/or serious adverse event used to collect adverse event information does not differ from that of the clinicaltrials.gov.
|
0.00%
0/3 • 3.8 years
The definition of adverse event and/or serious adverse event used to collect adverse event information does not differ from that of the clinicaltrials.gov.
|
8.0%
2/25 • Number of events 2 • 3.8 years
The definition of adverse event and/or serious adverse event used to collect adverse event information does not differ from that of the clinicaltrials.gov.
|
Additional Information
Erlinda M. Gordon, MD/Principal Investigator
Sarcoma Oncology Research Center
Phone: 310-552-9999
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place