Trial Outcomes & Findings for ABC294640 (Opaganib) in Refractory / Relapsed Multiple Myeloma (NCT NCT02757326)

Last Updated: 2021-06-18

Results Overview

Evaluation of three doses of opaganib - 250 mg bid, 500 mg bid and 750 mg bid to determine the maximum tolerated dose (MTD) based upon the dose limiting toxicity (DLT) using a Bayesian model averaging continual reassessment method and is the dose at which the estimated probability of toxicity is closest to the target probability 0.33 among all doses.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

13 participants

Primary outcome timeframe

6 months

Results posted on

2021-06-18

Participant Flow

Participant milestones

Participant milestones
Measure	250 mg Unblinded Phase 1b dose-finding study with dose escalation of study drug ABC294640 (Opaganib). Once a subject was determined to be eligible for the study, the subject was enrolled in the dose escalation Phase 1b study testing ABC294640 at 250 mg twice a day (bis in die). A cycle of treatment was defined as 28 days and doses were given initially under fasting conditions. Subsequent to a food effect study, treatment was given after a light to moderate meal.	500 mg Unblinded Phase 1b dose-finding study with dose escalation of study drug ABC294640. Once a subject was determined to be eligible for the study, the subject was enrolled in the dose escalation Phase 1b study testing ABC294640 at 500 mg twice a day). A cycle of treatment was defined as 28 days and doses were given initially under fasting conditions. Subsequent to a food effect study, treatment was given after a light to moderate meal.	750 mg Unblinded Phase 1b dose-finding study with dose escalation of study drug ABC294640. Once a subject was determined to be eligible for the study, the subject was enrolled in the dose escalation Phase 1b study testing ABC294640 doses at 750 mg twice a day ). A cycle of treatment was defined as 28 days and doses were given initially under fasting conditions. Subsequent to a food effect study, treatment was given after a light to moderate meal.
Overall Study STARTED	3	4	6
Overall Study COMPLETED	3	4	6
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

ABC294640 (Opaganib) in Refractory / Relapsed Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1b - 250 mg BID n=3 Participants For Phase 1b, ABC294640 was dosed at 250 BID given continuously. The dose was given under fasting conditions (at least 1 hour before or 2 hours after eating). One cycle is 28 days of treatment.	Phase 1b - 500 mg BID n=4 Participants For Phase 1b, ABC294640 was dosed at 500 BID given continuously. The dose was given under fasting conditions (at least 1 hour before or 2 hours after eating). One cycle is 28 days of treatment	Phase 1b - 750 mg BID n=6 Participants For Phase 1b, ABC294640 was dosed at 750 mg BID given continuously. The dose was given under fasting conditions (at least 1 hour before or 2 hours after eating). One cycle is 28 days of treatment	Total n=13 Participants Total of all reporting groups
Age, Continuous	70.0 years STANDARD_DEVIATION 4.58 • n=5 Participants	75.8 years STANDARD_DEVIATION 13.94 • n=7 Participants	63.8 years STANDARD_DEVIATION 6.94 • n=5 Participants	68.9 years STANDARD_DEVIATION 10.05 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants	7 Participants n=4 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
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 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
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 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
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
Region of Enrollment United States	3 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants	13 participants n=4 Participants
Baseline ECOG (Eastern Cooperative Oncology Group)Status ECOG 0	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Baseline ECOG (Eastern Cooperative Oncology Group)Status ECOG 1	2 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	9 Participants n=4 Participants
Baseline ECOG (Eastern Cooperative Oncology Group)Status ECOG 2	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Safety population

Outcome measures

Outcome measures
Measure	Opaganib n=13 Participants Unblinded Phase 1b dose-finding study with dose escalation of study drug ABC294640. Once a subject was determined to be eligible for the study, the subject was enrolled in the dose escalation Phase 1b study testing ABC294640 at 250, 500 and 750 mg twice a day. A cycle of treatment was defined as 28 days and doses were given initially under fasting conditions. Subsequent to a food effect study, treatment was given after a light to moderate meal.	ABC294640 500 mg BID ABC294640 250 mg BID given continuously	ABC294640 750 mg BID ABC294640 750 mg BID given continuously
Maximum Tolerated Dose	NA mg The maximum tolerated dose was not reached in the study	—	—

SECONDARY outcome

Timeframe: After 3 cycles (12 weeks) of treatment

Population: Intent to treat

Stable disease, partial response, complete response or disease progression.

Outcome measures

Outcome measures
Measure	Opaganib n=3 Participants Unblinded Phase 1b dose-finding study with dose escalation of study drug ABC294640. Once a subject was determined to be eligible for the study, the subject was enrolled in the dose escalation Phase 1b study testing ABC294640 at 250, 500 and 750 mg twice a day. A cycle of treatment was defined as 28 days and doses were given initially under fasting conditions. Subsequent to a food effect study, treatment was given after a light to moderate meal.	ABC294640 500 mg BID n=4 Participants ABC294640 250 mg BID given continuously	ABC294640 750 mg BID n=6 Participants ABC294640 750 mg BID given continuously
To Assess the Antitumor Activity of Single Agent Opaganib in Patients With Refractory or Relapsed Multiple Myeloma After 3 Cycles of Treatment.	0 Participants	2 Participants	0 Participants

SECONDARY outcome

Timeframe: 12 months

Population: All participants receiving any amount of study drug

For the phase 1b portion of the trial, a dose-limiting toxicity (DLT) was defined as an adverse event at least possibly related to the study medication: Non-hematologic DLT is defined as any Grade 3 or greater ADR (adverse drug reaction), except symptomatic AEs such as nausea, vomiting, and diarrhea which could be reduced to less than Grade 3 within 72 hours with standard supportive measures (i.e., antiemetics and antidiarrheals). Hematologic DLT is defined as * Grade 4 neutropenia or thrombocytopenia that lasts more than 7 days after the last dose of study drug * or greater than or equal to Grade 3 thrombocytopenia in the presence of greater than or equal to Grade 3 hemorrhage of any organ/site * or any Grade 5 hematologic toxicity

Outcome measures

Outcome measures
Measure	Opaganib n=3 Participants Unblinded Phase 1b dose-finding study with dose escalation of study drug ABC294640. Once a subject was determined to be eligible for the study, the subject was enrolled in the dose escalation Phase 1b study testing ABC294640 at 250, 500 and 750 mg twice a day. A cycle of treatment was defined as 28 days and doses were given initially under fasting conditions. Subsequent to a food effect study, treatment was given after a light to moderate meal.	ABC294640 500 mg BID n=4 Participants ABC294640 250 mg BID given continuously	ABC294640 750 mg BID n=6 Participants ABC294640 750 mg BID given continuously
Number of Patients With Dose Limiting Toxicity	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 8 hours

To determine the Cmax of ABC294640 following administration of the drug.

Outcome measures

Outcome measures
Measure	Opaganib n=3 Participants Unblinded Phase 1b dose-finding study with dose escalation of study drug ABC294640. Once a subject was determined to be eligible for the study, the subject was enrolled in the dose escalation Phase 1b study testing ABC294640 at 250, 500 and 750 mg twice a day. A cycle of treatment was defined as 28 days and doses were given initially under fasting conditions. Subsequent to a food effect study, treatment was given after a light to moderate meal.	ABC294640 500 mg BID n=4 Participants ABC294640 250 mg BID given continuously	ABC294640 750 mg BID n=6 Participants ABC294640 750 mg BID given continuously
Maximum Concentration (Cmax) of ABC294640	5.6 mcg/hr/mL Standard Deviation 1.7	12.5 mcg/hr/mL Standard Deviation 2.5	25.8 mcg/hr/mL Standard Deviation 3

Adverse Events

250 mg Phase 1b

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

500 mg Phase 1b

Serious events: 3 serious events

Other events: 4 other events

Deaths: 0 deaths

750 mg Phase 1b

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	250 mg Phase 1b n=3 participants at risk For Phase 1b, ABC294640 was dosed at 250 BID given continuously. The dose was given under fasting conditions (at least 1 hour before or 2 hours after eating). One cycle is 28 days of treatment.	500 mg Phase 1b n=4 participants at risk For Phase 1b, ABC294640 was dosed at 500 BID given continuously. The dose was given under fasting conditions (at least 1 hour before or 2 hours after eating). One cycle is 28 days of treatment.	750 mg Phase 1b n=6 participants at risk For Phase 1b, ABC294640 was dosed at 750 BID given continuously. The dose was given under fasting conditions (at least 1 hour before or 2 hours after eating). One cycle is 28 days of treatment.
Psychiatric disorders ALTERED MENTAL STATUS	33.3% 1/3 • Number of events 1 • Up to 20.5 weeks Treatment emergent adverse events (TEAE) were any event not present before exposure to study medication or any event already present that worsens in either intensity or frequency following exposure to study drug.	25.0% 1/4 • Number of events 1 • Up to 20.5 weeks Treatment emergent adverse events (TEAE) were any event not present before exposure to study medication or any event already present that worsens in either intensity or frequency following exposure to study drug.	0.00% 0/6 • Up to 20.5 weeks Treatment emergent adverse events (TEAE) were any event not present before exposure to study medication or any event already present that worsens in either intensity or frequency following exposure to study drug.
General disorders Pain	0.00% 0/3 • Up to 20.5 weeks Treatment emergent adverse events (TEAE) were any event not present before exposure to study medication or any event already present that worsens in either intensity or frequency following exposure to study drug.	25.0% 1/4 • Number of events 1 • Up to 20.5 weeks Treatment emergent adverse events (TEAE) were any event not present before exposure to study medication or any event already present that worsens in either intensity or frequency following exposure to study drug.	0.00% 0/6 • Up to 20.5 weeks Treatment emergent adverse events (TEAE) were any event not present before exposure to study medication or any event already present that worsens in either intensity or frequency following exposure to study drug.
Nervous system disorders Depressed level of consciousness	0.00% 0/3 • Up to 20.5 weeks Treatment emergent adverse events (TEAE) were any event not present before exposure to study medication or any event already present that worsens in either intensity or frequency following exposure to study drug.	25.0% 1/4 • Number of events 1 • Up to 20.5 weeks Treatment emergent adverse events (TEAE) were any event not present before exposure to study medication or any event already present that worsens in either intensity or frequency following exposure to study drug.	0.00% 0/6 • Up to 20.5 weeks Treatment emergent adverse events (TEAE) were any event not present before exposure to study medication or any event already present that worsens in either intensity or frequency following exposure to study drug.
Gastrointestinal disorders Colitis	0.00% 0/3 • Up to 20.5 weeks Treatment emergent adverse events (TEAE) were any event not present before exposure to study medication or any event already present that worsens in either intensity or frequency following exposure to study drug.	25.0% 1/4 • Number of events 1 • Up to 20.5 weeks Treatment emergent adverse events (TEAE) were any event not present before exposure to study medication or any event already present that worsens in either intensity or frequency following exposure to study drug.	0.00% 0/6 • Up to 20.5 weeks Treatment emergent adverse events (TEAE) were any event not present before exposure to study medication or any event already present that worsens in either intensity or frequency following exposure to study drug.
Gastrointestinal disorders Constipation	0.00% 0/3 • Up to 20.5 weeks Treatment emergent adverse events (TEAE) were any event not present before exposure to study medication or any event already present that worsens in either intensity or frequency following exposure to study drug.	25.0% 1/4 • Number of events 1 • Up to 20.5 weeks Treatment emergent adverse events (TEAE) were any event not present before exposure to study medication or any event already present that worsens in either intensity or frequency following exposure to study drug.	0.00% 0/6 • Up to 20.5 weeks Treatment emergent adverse events (TEAE) were any event not present before exposure to study medication or any event already present that worsens in either intensity or frequency following exposure to study drug.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/3 • Up to 20.5 weeks Treatment emergent adverse events (TEAE) were any event not present before exposure to study medication or any event already present that worsens in either intensity or frequency following exposure to study drug.	25.0% 1/4 • Number of events 1 • Up to 20.5 weeks Treatment emergent adverse events (TEAE) were any event not present before exposure to study medication or any event already present that worsens in either intensity or frequency following exposure to study drug.	0.00% 0/6 • Up to 20.5 weeks Treatment emergent adverse events (TEAE) were any event not present before exposure to study medication or any event already present that worsens in either intensity or frequency following exposure to study drug.
Cardiac disorders Cardiac arrest	0.00% 0/3 • Up to 20.5 weeks Treatment emergent adverse events (TEAE) were any event not present before exposure to study medication or any event already present that worsens in either intensity or frequency following exposure to study drug.	25.0% 1/4 • Number of events 1 • Up to 20.5 weeks Treatment emergent adverse events (TEAE) were any event not present before exposure to study medication or any event already present that worsens in either intensity or frequency following exposure to study drug.	0.00% 0/6 • Up to 20.5 weeks Treatment emergent adverse events (TEAE) were any event not present before exposure to study medication or any event already present that worsens in either intensity or frequency following exposure to study drug.
Musculoskeletal and connective tissue disorders Pathological fracture	0.00% 0/3 • Up to 20.5 weeks Treatment emergent adverse events (TEAE) were any event not present before exposure to study medication or any event already present that worsens in either intensity or frequency following exposure to study drug.	0.00% 0/4 • Up to 20.5 weeks Treatment emergent adverse events (TEAE) were any event not present before exposure to study medication or any event already present that worsens in either intensity or frequency following exposure to study drug.	16.7% 1/6 • Number of events 1 • Up to 20.5 weeks Treatment emergent adverse events (TEAE) were any event not present before exposure to study medication or any event already present that worsens in either intensity or frequency following exposure to study drug.

Other adverse events

Additional Information

Yubin Kang, M.D., Principal Investigator

Duke University Medical Center, Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy

Phone: (919) 668-2331

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place