Trial Outcomes & Findings for Phase I/II Study of Lenalidomide Plus Pembrolizumab in Patients With Solid Tumors With Expansion in Non-small Cell Lung Cancer (NCT NCT02963610)

NCT ID: NCT02963610

Last Updated: 2021-12-30

Results Overview

Maximum tolerated dose of Lenalidomide

• Recruitment status: TERMINATED
• Study phase: PHASE1/PHASE2
• Target enrollment: 3 participants
• Primary outcome timeframe: Day 22 of cycle 1
• Results posted on: 2021-12-30

Participant Flow

Participant milestones

Measure	Pembrolizumab, Lenalidomide Phase I The treatment will be given on a 21-day cycle, with a dose of pembrolizumab given on day1(IV) and doses of lenalidomide given on day 1-14 (orally). The dose of pembrolizumab will be fixed at 200 mg. The dose of lenalidomide will depend upon the patient cohort. Cohort 1 will receive 10mg, Cohort II will receive 15mg and cohort 3 will receive 20mg of lenalidomide. Phase II The treatment will be given on a 21-day cycle, with a dose of pembrolizumab given on day1(IV) and doses of lenalidomide given on day 1-14 (orally). The dose of pembrolizumab will be fixed at 200 mg. Maximum Tolerated Dose (MTD) of lenalidomide as determined by the Phase I study will be given in Phase II study. Lenalidomide: Lenalidomide is a thalidomide analogue with immunomodulatory, anti-angiogenic, and antineoplastic effects. It is administered as a pill taken orally. It has completed phase III study evaluation and has FDA indications for use in certain patients with multiple myeloma, myelodysplastic syndrome, and mantle cell lymphoma. Pembrolizumab: Pembrolizumab is a humanized IgG4 monoclonal antibody which targets the PD-1 receptor, thus inhibiting the interaction between PD-1 and its ligands, PD-L1 and PD-L2 respectively. It is administered as an IV infusion. This drug has several studies in patients with solid tumors and currently has an FDA indication for use in patients with melanoma and non-small cell lung cancer.
Overall Study STARTED	3
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure

Pembrolizumab, Lenalidomide Phase I The treatment will be given on a 21-day cycle, with a dose of pembrolizumab given on day1(IV) and doses of lenalidomide given on day 1-14 (orally). The dose of pembrolizumab will be fixed at 200 mg. The dose of lenalidomide will depend upon the patient cohort. Cohort 1 will receive 10mg, Cohort II will receive 15mg and cohort 3 will receive 20mg of lenalidomide. Phase II The treatment will be given on a 21-day cycle, with a dose of pembrolizumab given on day1(IV) and doses of lenalidomide given on day 1-14 (orally). The dose of pembrolizumab will be fixed at 200 mg. Maximum Tolerated Dose (MTD) of lenalidomide as determined by the Phase I study will be given in Phase II study. Lenalidomide: Lenalidomide is a thalidomide analogue with immunomodulatory, anti-angiogenic, and antineoplastic effects. It is administered as a pill taken orally. It has completed phase III study evaluation and has FDA indications for use in certain patients with multiple myeloma, myelodysplastic syndrome, and mantle cell lymphoma. Pembrolizumab: Pembrolizumab is a humanized IgG4 monoclonal antibody which targets the PD-1 receptor, thus inhibiting the interaction between PD-1 and its ligands, PD-L1 and PD-L2 respectively. It is administered as an IV infusion. This drug has several studies in patients with solid tumors and currently has an FDA indication for use in patients with melanoma and non-small cell lung cancer.

Overall Study Study terminated prematurely due to funding/support being withdrawn by grantor. No analyses occurred

3

Baseline Characteristics

Phase I/II Study of Lenalidomide Plus Pembrolizumab in Patients With Solid Tumors With Expansion in Non-small Cell Lung Cancer

Baseline characteristics by cohort

Measure	Pembrolizumab, Lenalidomide n=3 Participants Phase I The treatment will be given on a 21-day cycle, with a dose of pembrolizumab given on day1(IV) and doses of lenalidomide given on day 1-14 (orally). The dose of pembrolizumab will be fixed at 200 mg. The dose of lenalidomide will depend upon the patient cohort. Cohort 1 will receive 10mg, Cohort II will receive 15mg and cohort 3 will receive 20mg of lenalidomide. Phase II The treatment will be given on a 21-day cycle, with a dose of pembrolizumab given on day1(IV) and doses of lenalidomide given on day 1-14 (orally). The dose of pembrolizumab will be fixed at 200 mg. Maximum Tolerated Dose (MTD) of lenalidomide as determined by the Phase I study will be given in Phase II study. Lenalidomide: Lenalidomide is a thalidomide analogue with immunomodulatory, anti-angiogenic, and antineoplastic effects. It is administered as a pill taken orally. It has completed phase III study evaluation and has FDA indications for use in certain patients with multiple myeloma, myelodysplastic syndrome, and mantle cell lymphoma. Pembrolizumab: Pembrolizumab is a humanized IgG4 monoclonal antibody which targets the PD-1 receptor, thus inhibiting the interaction between PD-1 and its ligands, PD-L1 and PD-L2 respectively. It is administered as an IV infusion. This drug has several studies in patients with solid tumors and currently has an FDA indication for use in patients with melanoma and non-small cell lung cancer.
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=93 Participants
Age, Categorical >=65 years	2 Participants n=93 Participants
Sex: Female, Male Female	2 Participants n=93 Participants
Sex: Female, Male Male	1 Participants n=93 Participants
Race/Ethnicity, Customized White Non-Hispanic	2 Participants n=93 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=93 Participants
Region of Enrollment United States	3 Participants n=93 Participants

PRIMARY outcome

Timeframe: Day 22 of cycle 1

Population: Study terminated prematurely due to funding/support being withdrawn by grantor. No analyses occurred

Maximum tolerated dose of Lenalidomide

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: up to 3 years

Population: Study terminated prematurely due to funding/support being withdrawn by grantor. No analyses occurred

PFS

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: upto 2 years

Population: Study terminated prematurely due to funding/support being withdrawn by grantor. No analyses occurred

ORR

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: upto 2 years

Population: Study terminated prematurely due to funding/support being withdrawn by grantor. No analyses occurred

PD-1 expression will be used to correlate with the treatment response

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: upto 2 years

Population: Study terminated prematurely due to funding/support being withdrawn by grantor. No analyses occurred

Amount of CD45, CD3, CD4, CD8 (T cells), CD19 (B cells), CD14, CD16 (monocytes), CD56 (NK cells), CD11c, HLA-DR, CD303, CD66b (myeloid - DCs and granulocytes).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: upto 2 years

Population: Study terminated prematurely due to funding/support being withdrawn by grantor. No analyses occurred

Th1/Tc1 responses ( IFN-g, TNF, IL-2), Th2/Tc1 responses (IL-4, IL-5, IL-10), pro-inflammatory innate responses (IFN-α, IL-1β, IL-6, IL-17), homeostatic lymphocyte expansion (IL-7, IL-15), and chemotaxis of immune cells (IP-10, MCP-1, MIP-1α, MIP-1β, RANTES) will be measured

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: upto 2 years

Population: Study terminated prematurely due to funding/support being withdrawn by grantor. No analyses occurred

CD107A expression after 2 hour co-culture with the EBV-transformed B cell line, 721.221, without and with rituximab (ADCC conditions).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: upto 2 years

Population: Study terminated prematurely due to funding/support being withdrawn by grantor. No analyses occurred

Activation markers will include CD69, CD25, HLA-DR, IL-15Ra, perforin, Ki67, NKp44, CD57

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: upto 2 years

Population: Study terminated prematurely due to funding/support being withdrawn by grantor. No analyses occurred

Expression of genes involved in immune responses

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: upto 2 years

Population: Study terminated prematurely due to funding/support being withdrawn by grantor. No analyses occurred

number of patients that overcome the resistance of previous anti-pD-1 therapy

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: upto 2 years

Population: Study terminated prematurely due to funding/support being withdrawn by grantor. No analyses occurred

Differentiation status of CD4 and CD8 T cells (naïve/effector memory/central memory/regulatory/delta-gamma TCR) as defined by: CD62L, CD45RA, CD127, CD25.

Outcome measures

Outcome data not reported

Adverse Events

Pembrolizumab, Lenalidomide

Serious events: 0 serious events

Other events: 3 other events

Deaths: 2 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Pembrolizumab, Lenalidomide n=3 participants at risk Phase I The treatment will be given on a 21-day cycle, with a dose of pembrolizumab given on day1(IV) and doses of lenalidomide given on day 1-14 (orally). The dose of pembrolizumab will be fixed at 200 mg. The dose of lenalidomide will depend upon the patient cohort. Cohort 1 will receive 10mg, Cohort II will receive 15mg and cohort 3 will receive 20mg of lenalidomide. Phase II The treatment will be given on a 21-day cycle, with a dose of pembrolizumab given on day1(IV) and doses of lenalidomide given on day 1-14 (orally). The dose of pembrolizumab will be fixed at 200 mg. Maximum Tolerated Dose (MTD) of lenalidomide as determined by the Phase I study will be given in Phase II study. Lenalidomide: Lenalidomide is a thalidomide analogue with immunomodulatory, anti-angiogenic, and antineoplastic effects. It is administered as a pill taken orally. It has completed phase III study evaluation and has FDA indications for use in certain patients with multiple myeloma, myelodysplastic syndrome, and mantle cell lymphoma. Pembrolizumab: Pembrolizumab is a humanized IgG4 monoclonal antibody which targets the PD-1 receptor, thus inhibiting the interaction between PD-1 and its ligands, PD-L1 and PD-L2 respectively. It is administered as an IV infusion. This drug has several studies in patients with solid tumors and currently has an FDA indication for use in patients with melanoma and non-small cell lung cancer.
Gastrointestinal disorders Constipation	66.7% 2/3 • 4 months
Gastrointestinal disorders Abdominal distension	66.7% 2/3 • 4 months
Gastrointestinal disorders Diarrhea	33.3% 1/3 • 4 months
Gastrointestinal disorders Fecal incontinence	33.3% 1/3 • 4 months
Gastrointestinal disorders Nausea	33.3% 1/3 • 4 months
Metabolism and nutrition disorders Anorexia	33.3% 1/3 • 4 months
Metabolism and nutrition disorders Hypoalkemia	33.3% 1/3 • 4 months
Metabolism and nutrition disorders Hyponatremia	33.3% 1/3 • 4 months
Respiratory, thoracic and mediastinal disorders Cough	33.3% 1/3 • 4 months
Respiratory, thoracic and mediastinal disorders Postnasal drip	33.3% 1/3 • 4 months
Respiratory, thoracic and mediastinal disorders Sore throat	33.3% 1/3 • 4 months
Skin and subcutaneous tissue disorders Pruritis	66.7% 2/3 • 4 months
Endocrine disorders Hypothyroidism	33.3% 1/3 • 4 months
Eye disorders Photophobia	33.3% 1/3 • 4 months
Eye disorders Watering eyes	33.3% 1/3 • 4 months
General disorders Chills	33.3% 1/3 • 4 months
General disorders Edema limbs	33.3% 1/3 • 4 months
General disorders Fatigue	33.3% 1/3 • 4 months
Investigations Weight loss	33.3% 1/3 • 4 months
Nervous system disorders Dizziness	33.3% 1/3 • 4 months
Renal and urinary disorders Urinary frequency	33.3% 1/3 • 4 months

Additional Information

Hossein Borghaei, DO, MS

Fox Chase Cancer Center

Phone: 215-214-4297

Email: Hossein.Borghaei@fccc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place