Trial Outcomes & Findings for Pembrolizumab + Lenalidomide Post Autologous Stem Cell Transplant (ASCT) in High-risk Multiple Myeloma (MM) (NCT NCT02906332)

Results Overview

PFS will be assessed from the date of ASCT, with day 0 defined as date of stem cell infusion (if tandem transplant the 2nd of 2 transplants will be used) until the date of progression, defined as the date at which the patient starts the next line of therapy or the date of death.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

12 participants

Primary outcome timeframe

Up to 3 years

Results posted on

2023-08-22

Participant Flow

Participant milestones

Participant milestones
Measure	Pembrolizumab + Lenalidomide This is an open label study. * Pembrolizumab 200 mg IV every 3 weeks and lenalidomide 25 mg po daily x 14 days and dexamethasone 40 mg po once weekly for a 21-day cycle x 2 cycles. * This is followed by pembrolizumab 200 mg every 3 weeks and lenalidomide 25 mg po daily x 14 days for a 21-day cycle x 2 cycles for a total of 4 cycles. Pembrolizumab: Pembrolizumab 200 mg IV every 3 weeks x 2 cycles. This is followed by followed by pembrolizumab 200 mg IV every 3 weeks for 2 additional cycles. Lenalidomide: Lenalidomide 25 mg po daily x 14 days once weekly for a 21-day cycle x 2 cycles. This is followed by lenalidomide 25 mg po daily x 14 days for a 21-day cycle x 2 cycles for 2 additional cycles. Dexamethasone: Dexamethasone 40 mg po once weekly for a 21-day cycle x 2 cycles only.
Overall Study STARTED	12
Overall Study COMPLETED	11
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Pembrolizumab + Lenalidomide This is an open label study. * Pembrolizumab 200 mg IV every 3 weeks and lenalidomide 25 mg po daily x 14 days and dexamethasone 40 mg po once weekly for a 21-day cycle x 2 cycles. * This is followed by pembrolizumab 200 mg every 3 weeks and lenalidomide 25 mg po daily x 14 days for a 21-day cycle x 2 cycles for a total of 4 cycles. Pembrolizumab: Pembrolizumab 200 mg IV every 3 weeks x 2 cycles. This is followed by followed by pembrolizumab 200 mg IV every 3 weeks for 2 additional cycles. Lenalidomide: Lenalidomide 25 mg po daily x 14 days once weekly for a 21-day cycle x 2 cycles. This is followed by lenalidomide 25 mg po daily x 14 days for a 21-day cycle x 2 cycles for 2 additional cycles. Dexamethasone: Dexamethasone 40 mg po once weekly for a 21-day cycle x 2 cycles only.
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Pembrolizumab + Lenalidomide Post Autologous Stem Cell Transplant (ASCT) in High-risk Multiple Myeloma (MM)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pembrolizumab + Lenalidomide n=12 Participants This is an open label study. * Pembrolizumab 200 mg IV every 3 weeks and lenalidomide 25 mg po daily x 14 days and dexamethasone 40 mg po once weekly for a 21-day cycle x 2 cycles. * This is followed by pembrolizumab 200 mg every 3 weeks and lenalidomide 25 mg po daily x 14 days for a 21-day cycle x 2 cycles for a total of 4 cycles. Pembrolizumab: Pembrolizumab 200 mg IV every 3 weeks x 2 cycles. This is followed by followed by pembrolizumab 200 mg IV every 3 weeks for 2 additional cycles. Lenalidomide: Lenalidomide 25 mg po daily x 14 days once weekly for a 21-day cycle x 2 cycles. This is followed by lenalidomide 25 mg po daily x 14 days for a 21-day cycle x 2 cycles for 2 additional cycles. Dexamethasone: Dexamethasone 40 mg po once weekly for a 21-day cycle x 2 cycles only.
Age, Customized Age	67.2 years n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants
Race/Ethnicity, Customized White	10 Participants n=5 Participants
Race/Ethnicity, Customized Non-White	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 3 years

PFS will be assessed from the date of ASCT, with day 0 defined as date of stem cell infusion (if tandem transplant the 2nd of 2 transplants will be used) until the date of progression, defined as the date at which the patient starts the next line of therapy or the date of death.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenalidomide n=11 Participants This is an open label study. * Pembrolizumab 200 mg IV every 3 weeks and lenalidomide 25 mg po daily x 14 days and dexamethasone 40 mg po once weekly for a 21-day cycle x 2 cycles. * This is followed by pembrolizumab 200 mg every 3 weeks and lenalidomide 25 mg po daily x 14 days for a 21-day cycle x 2 cycles for a total of 4 cycles. Pembrolizumab: Pembrolizumab 200 mg IV every 3 weeks x 2 cycles. This is followed by followed by pembrolizumab 200 mg IV every 3 weeks for 2 additional cycles. Lenalidomide: Lenalidomide 25 mg po daily x 14 days once weekly for a 21-day cycle x 2 cycles. This is followed by lenalidomide 25 mg po daily x 14 days for a 21-day cycle x 2 cycles for 2 additional cycles. Dexamethasone: Dexamethasone 40 mg po once weekly for a 21-day cycle x 2 cycles only.
Progression Free Survival (PFS)	27.6 months Interval 10.0 to 30.1

SECONDARY outcome

Timeframe: Up to 3 years

Safety will be assessed by quantifying the toxicities and grades experienced by subjects who have received pembrolizumab (MK-3475), lenalidomide and dexamethasone, including serious adverse events (SAEs). Result reflects count of participants who experienced an SAE.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenalidomide n=12 Participants This is an open label study. * Pembrolizumab 200 mg IV every 3 weeks and lenalidomide 25 mg po daily x 14 days and dexamethasone 40 mg po once weekly for a 21-day cycle x 2 cycles. * This is followed by pembrolizumab 200 mg every 3 weeks and lenalidomide 25 mg po daily x 14 days for a 21-day cycle x 2 cycles for a total of 4 cycles. Pembrolizumab: Pembrolizumab 200 mg IV every 3 weeks x 2 cycles. This is followed by followed by pembrolizumab 200 mg IV every 3 weeks for 2 additional cycles. Lenalidomide: Lenalidomide 25 mg po daily x 14 days once weekly for a 21-day cycle x 2 cycles. This is followed by lenalidomide 25 mg po daily x 14 days for a 21-day cycle x 2 cycles for 2 additional cycles. Dexamethasone: Dexamethasone 40 mg po once weekly for a 21-day cycle x 2 cycles only.
Number of Participants Serious Adverse Events	1 Participants

SECONDARY outcome

Timeframe: Every 3 weeks (day 1 of every 21-day treatment cycle +/- 7 days) through 12 weeks.

Assessed by the investigator per International Myeloma Working Group criteria(IMWG) uniform response criteria. Result reflects number of participants whose best overall response qualified as sCR, CR, or VGPR in 2 year follow up period.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenalidomide n=11 Participants This is an open label study. * Pembrolizumab 200 mg IV every 3 weeks and lenalidomide 25 mg po daily x 14 days and dexamethasone 40 mg po once weekly for a 21-day cycle x 2 cycles. * This is followed by pembrolizumab 200 mg every 3 weeks and lenalidomide 25 mg po daily x 14 days for a 21-day cycle x 2 cycles for a total of 4 cycles. Pembrolizumab: Pembrolizumab 200 mg IV every 3 weeks x 2 cycles. This is followed by followed by pembrolizumab 200 mg IV every 3 weeks for 2 additional cycles. Lenalidomide: Lenalidomide 25 mg po daily x 14 days once weekly for a 21-day cycle x 2 cycles. This is followed by lenalidomide 25 mg po daily x 14 days for a 21-day cycle x 2 cycles for 2 additional cycles. Dexamethasone: Dexamethasone 40 mg po once weekly for a 21-day cycle x 2 cycles only.
Evaluation of Stringent Complete Response, Complete Response, and Very Good Partial Response Rate (sCR + CR + VGPR Rate).	11 Participants

SECONDARY outcome

Timeframe: Time from Day 0 (transplant) and date of enrollment to study completion (through 12 weeks) by investigator assessment.

Assessed at 12 months; Subjects without documented PD or death will be censored at the last disease assessment date. Those who died without documented PD will be censored at the time of death. Result reflects count of participants who had progressed at 12 months.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenalidomide n=11 Participants This is an open label study. * Pembrolizumab 200 mg IV every 3 weeks and lenalidomide 25 mg po daily x 14 days and dexamethasone 40 mg po once weekly for a 21-day cycle x 2 cycles. * This is followed by pembrolizumab 200 mg every 3 weeks and lenalidomide 25 mg po daily x 14 days for a 21-day cycle x 2 cycles for a total of 4 cycles. Pembrolizumab: Pembrolizumab 200 mg IV every 3 weeks x 2 cycles. This is followed by followed by pembrolizumab 200 mg IV every 3 weeks for 2 additional cycles. Lenalidomide: Lenalidomide 25 mg po daily x 14 days once weekly for a 21-day cycle x 2 cycles. This is followed by lenalidomide 25 mg po daily x 14 days for a 21-day cycle x 2 cycles for 2 additional cycles. Dexamethasone: Dexamethasone 40 mg po once weekly for a 21-day cycle x 2 cycles only.
Number of Participants Who Progressed at 12 Months	10 Participants

SECONDARY outcome

Timeframe: Interval between date of first response and date of study completion (through 12 weeks)

Population: The FDA required enrollment to stop and patients to be removed from treatment due to updated risks of the investigational product. Following removal of the study data was not collected and patients were not analyzed due to this early termination of study intervention.

Assessed by the investigator per International Myeloma Working Group criteria(IMWG) uniform response criteria. Result reflects count of participants who did not have progressive disease at 2 years.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Bone marrow aspirate specimens will be obtained at screening and at week 15 (completion of cycle 4).

Comparison of change from baseline in bone marrow aspirate/biopsy PD-L1 expression between responders with longer duration of response and non-responders or responders with a short duration of response will be performed using mixed regression analysis. Longitudinal analysis of bone marrow aspirate/biopsy PD-L1 expression over time will be examined using mixed model repeated measure design with levels observed serially over time and response type (long responders vs short responders/non-response) as a fixed variable.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Obtained monthly through week 12 (cycle 4 day 1).

Assays for these studies include flow cytometry, TCR Immunoseq for Vbeta CDR3 highest frequency specificities, real-time PCR analysis and multiplex cytokine ELISA. These data will be aggregated before and after treatment in responders versus non-responders.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Obtained monthly through week 12 (cycle 4 day 1).

Assays for these studies include flow cytometry, TCR Immunoseq for Vbeta CDR3 highest frequency specificities, and real-time PCR analysis. T cells (CD8+) data will be aggregated before and after treatment in responders versus non-responders.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Obtained monthly through week 12 (cycle 4 day 1).

Multiplex cytokine ELISA studies will assess inflammatory cytokine (TNF-alpha, IL-2, IL-4, IL-6, IL-10) data and will be aggregated before and after treatment in responders versus non-responders.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Stool specimens at screening or cycle 1, day 1, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1, at completion of cycle 4, and at 90 days post treatment or start of new anti cancer therapy. Stool samples will also be collected at confirmation of response.

A 16S ribosomal RNA (rRNA) miSeq Illumina platform will be used for overall microbial composition and quantitative real-time PCR analysis will validate the specific microbial strains identified by miSeq.

Outcome measures

Outcome data not reported

Adverse Events

Pembrolizumab + Lenalidomide

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Pembrolizumab + Lenalidomide n=12 participants at risk This is an open label study. * Pembrolizumab 200 mg IV every 3 weeks and lenalidomide 25 mg po daily x 14 days and dexamethasone 40 mg po once weekly for a 21-day cycle x 2 cycles. * This is followed by pembrolizumab 200 mg every 3 weeks and lenalidomide 25 mg po daily x 14 days for a 21-day cycle x 2 cycles for a total of 4 cycles. Pembrolizumab: Pembrolizumab 200 mg IV every 3 weeks x 2 cycles. This is followed by followed by pembrolizumab 200 mg IV every 3 weeks for 2 additional cycles. Lenalidomide: Lenalidomide 25 mg po daily x 14 days once weekly for a 21-day cycle x 2 cycles. This is followed by lenalidomide 25 mg po daily x 14 days for a 21-day cycle x 2 cycles for 2 additional cycles. Dexamethasone: Dexamethasone 40 mg po once weekly for a 21-day cycle x 2 cycles only.
Respiratory, thoracic and mediastinal disorders H. Influenza Pneumonia	8.3% 1/12 • Number of events 1 • Study Enrollment to Study Completion, up to 3 years

Other adverse events

Other adverse events
Measure	Pembrolizumab + Lenalidomide n=12 participants at risk This is an open label study. * Pembrolizumab 200 mg IV every 3 weeks and lenalidomide 25 mg po daily x 14 days and dexamethasone 40 mg po once weekly for a 21-day cycle x 2 cycles. * This is followed by pembrolizumab 200 mg every 3 weeks and lenalidomide 25 mg po daily x 14 days for a 21-day cycle x 2 cycles for a total of 4 cycles. Pembrolizumab: Pembrolizumab 200 mg IV every 3 weeks x 2 cycles. This is followed by followed by pembrolizumab 200 mg IV every 3 weeks for 2 additional cycles. Lenalidomide: Lenalidomide 25 mg po daily x 14 days once weekly for a 21-day cycle x 2 cycles. This is followed by lenalidomide 25 mg po daily x 14 days for a 21-day cycle x 2 cycles for 2 additional cycles. Dexamethasone: Dexamethasone 40 mg po once weekly for a 21-day cycle x 2 cycles only.
Blood and lymphatic system disorders Neutropenia	41.7% 5/12 • Study Enrollment to Study Completion, up to 3 years
Gastrointestinal disorders Constipation	16.7% 2/12 • Study Enrollment to Study Completion, up to 3 years
Gastrointestinal disorders Diarrhea	16.7% 2/12 • Study Enrollment to Study Completion, up to 3 years
Psychiatric disorders Fatigue	8.3% 1/12 • Study Enrollment to Study Completion, up to 3 years
Blood and lymphatic system disorders Increased ALT	8.3% 1/12 • Study Enrollment to Study Completion, up to 3 years
Respiratory, thoracic and mediastinal disorders Hypoxia	8.3% 1/12 • Study Enrollment to Study Completion, up to 3 years
Skin and subcutaneous tissue disorders Maculopapular Rash	8.3% 1/12 • Study Enrollment to Study Completion, up to 3 years

Additional Information

Joshua Zenreich

Hackensack Meridian Health

Phone: 15519964248

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place