Trial Outcomes & Findings for Trametinib and Akt Inhibitor GSK2141795 in Treating Patients With Relapsed or Refractory Multiple Myeloma (NCT NCT01989598)

Results Overview

"Per International Myeloma Working Group (IMWG) Criteria: Complete Response (CR), Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow; Partial Response (PR), \> 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by \>90% or to \< 200 mg/24 h; Overall Response (OR) = CR + PR."

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

25 participants

Primary outcome timeframe

Every 4 weeks until progression or death, whichever occurs first, an average of 9 months.

Results posted on

2022-03-02

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (Trametinib, Akt Inhibitor GSK2141795) Patients receive trametinib orally PO QD (once daily) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease or who achieve less than PR after 4 courses may also receive Akt inhibitor GSK2141795 PO daily on days 1-28. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Trametinib: Given PO Uprosertib: Given PO
Overall Study STARTED	25
Overall Study Dual Therapy With Trametinib and GSK2141795	12
Overall Study COMPLETED	25
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Trametinib, Akt Inhibitor GSK2141795) n=25 Participants Patients receive trametinib orally PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease or who achieve less than PR after 4 courses may also receive Akt inhibitor GSK2141795 PO daily on days 1-28. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Trametinib: Given PO Uprosertib: Given PO
Age, Categorical <=18 years	0 Participants n=25 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=25 Participants
Age, Categorical >=65 years	12 Participants n=25 Participants
Age, Continuous	64 years n=25 Participants
Sex: Female, Male Female	14 Participants n=25 Participants
Sex: Female, Male Male	11 Participants n=25 Participants
Region of Enrollment Canada	25 participants n=25 Participants

PRIMARY outcome

Timeframe: Every 4 weeks until progression or death, whichever occurs first, an average of 9 months.

"Per International Myeloma Working Group (IMWG) Criteria: Complete Response (CR), Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow; Partial Response (PR), \> 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by \>90% or to \< 200 mg/24 h; Overall Response (OR) = CR + PR."

Outcome measures

Outcome measures
Measure	Treatment (Trametinib) n=24 Participants Patients receive trametinib orally PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Treatment (Trametinib, Akt Inhibitor GSK2141795) n=11 Participants Patients who develop progressive disease on trametinib monotherapy or achieve less then a PR after 4 cycles of treatment will have the option to continue on trametinib with the addition of GSK2141795	Detection of BRAF Mutations Using cfDNA Ultra-deep sequencing will be performed on cfDNA to assess the feasibility of detecting mutations of BRAF from peripheral blood samples.
ORR Evidenced by Confirmed Response Rate, Defined as Number of Patients With Partial Response or Better by International Myeloma Working Group (IMWG) Criteria Divided by the Number of Patients in the Applicable Group (Biomarker Positive or Negative)	1 participants	2 participants	—

SECONDARY outcome

Timeframe: Time from the date of start of treatment to the date of documented progression (based on IMWG criteria) or death, whichever occurs first, due to any cause, assessed every 4 weeks, an average of 9 months.

Population: Note: 25 patients enrolled, however, one patient unevaluable was not included in analysis

Summarized for each cohort using the Kaplan-Meier method, from the date of start of treatment to the date of documented progression (based on IMWG criteria) or death due to any cause, assessed every 4 weeks

Outcome measures

Outcome measures
Measure	Treatment (Trametinib) n=24 Participants Patients receive trametinib orally PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Treatment (Trametinib, Akt Inhibitor GSK2141795) Patients who develop progressive disease on trametinib monotherapy or achieve less then a PR after 4 cycles of treatment will have the option to continue on trametinib with the addition of GSK2141795	Detection of BRAF Mutations Using cfDNA Ultra-deep sequencing will be performed on cfDNA to assess the feasibility of detecting mutations of BRAF from peripheral blood samples.
PFS	1.8 months Interval 0.9 to 3.2	—	—

SECONDARY outcome

Timeframe: From time measurement criteria are met for CR or PR (complete or partial response), (whichever recorded first) until first date that recurrent or progressive disease is objectively documented or to death due to multiple myeloma, assessed every 4 weeks

Population: Not reported. Data were not collected and not analyzed for this outcome measure.

Summarized for each cohort using the Kaplan-Meier method.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Every 4 weeks until progression or death, whichever occurs first, an average of 9 months.

Population: Trametinib monotherapy arm not applicable for this outcome measure

"Per International Myeloma Working Group (IMWG) Criteria: Complete Response (CR), Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow; Partial Response (PR), \> 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by \>90% or to \< 200 mg/24 h; Overall Response (OR) = CR + PR."

Outcome measures

Outcome measures
Measure	Treatment (Trametinib) Patients receive trametinib orally PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Treatment (Trametinib, Akt Inhibitor GSK2141795) n=11 Participants Patients who develop progressive disease on trametinib monotherapy or achieve less then a PR after 4 cycles of treatment will have the option to continue on trametinib with the addition of GSK2141795	Detection of BRAF Mutations Using cfDNA Ultra-deep sequencing will be performed on cfDNA to assess the feasibility of detecting mutations of BRAF from peripheral blood samples.
ORR After the Addition of AKT Inhibitor GSK2141795 to Trametinib in Patients Who Have Developed Progressive Disease or Have Achieved Less Than a PR	0 Participants	2 Participants	—

SECONDARY outcome

Timeframe: From time of treatment start until treatment completion, an average of 1 year

Reported by type, frequency, and severity.

Outcome measures

Outcome measures
Measure	Treatment (Trametinib) n=25 Participants Patients receive trametinib orally PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Treatment (Trametinib, Akt Inhibitor GSK2141795) n=12 Participants Patients who develop progressive disease on trametinib monotherapy or achieve less then a PR after 4 cycles of treatment will have the option to continue on trametinib with the addition of GSK2141795	Detection of BRAF Mutations Using cfDNA Ultra-deep sequencing will be performed on cfDNA to assess the feasibility of detecting mutations of BRAF from peripheral blood samples.
Incidence of Adverse Event Reactions Reported According to CTCAE v4.0	2 Adverse Events	4 Adverse Events	—

Adverse Events

Treatment (Trametinib, Akt Inhibitor GSK2141795)

Serious events: 15 serious events

Other events: 25 other events

Deaths: 7 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Trametinib, Akt Inhibitor GSK2141795) n=25 participants at risk Patients receive trametinib orally PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease or who achieve less than PR after 4 courses may also receive Akt inhibitor GSK2141795 PO daily on days 1-28. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Trametinib: Given PO Uprosertib: Given PO
Infections and infestations Sepsis	24.0% 6/25 • From treatment start until 4 weeks after treatment end or death (whichever occurs first), for each patient, an average of 1 year. Adverse events collected as per protocol using CTCAE version 4.0
Infections and infestations Lung infection	8.0% 2/25 • From treatment start until 4 weeks after treatment end or death (whichever occurs first), for each patient, an average of 1 year. Adverse events collected as per protocol using CTCAE version 4.0
Nervous system disorders Intracranial hemorrhage	8.0% 2/25 • From treatment start until 4 weeks after treatment end or death (whichever occurs first), for each patient, an average of 1 year. Adverse events collected as per protocol using CTCAE version 4.0
Neoplasms benign, malignant and unspecified (incl cysts and polyps) NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED	8.0% 2/25 • From treatment start until 4 weeks after treatment end or death (whichever occurs first), for each patient, an average of 1 year. Adverse events collected as per protocol using CTCAE version 4.0
Psychiatric disorders Confusion	12.0% 3/25 • From treatment start until 4 weeks after treatment end or death (whichever occurs first), for each patient, an average of 1 year. Adverse events collected as per protocol using CTCAE version 4.0

Other adverse events

Other adverse events
Measure	Treatment (Trametinib, Akt Inhibitor GSK2141795) n=25 participants at risk Patients receive trametinib orally PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease or who achieve less than PR after 4 courses may also receive Akt inhibitor GSK2141795 PO daily on days 1-28. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Trametinib: Given PO Uprosertib: Given PO
Investigations thrombocytopenia	52.0% 13/25 • From treatment start until 4 weeks after treatment end or death (whichever occurs first), for each patient, an average of 1 year. Adverse events collected as per protocol using CTCAE version 4.0
Gastrointestinal disorders Nausea	56.0% 14/25 • From treatment start until 4 weeks after treatment end or death (whichever occurs first), for each patient, an average of 1 year. Adverse events collected as per protocol using CTCAE version 4.0
Skin and subcutaneous tissue disorders Rash	68.0% 17/25 • From treatment start until 4 weeks after treatment end or death (whichever occurs first), for each patient, an average of 1 year. Adverse events collected as per protocol using CTCAE version 4.0

Additional Information

Dr. Suzanna Trudel

Princess Margaret Cancer Centre

Phone: 4169464501

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60