Trial Outcomes & Findings for Pembrolizumab and Afatinib in Patients With Non-small Cell Lung Cancer With Resistance to Erlotinib (NCT NCT02364609)

Last Updated: 2024-10-16

Results Overview

MTD is defined as the dose were less than two patients experienced a dose limiting toxicity. Dose limiting toxicities are defined in the protocol and graded per CTCAE 4.0.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

11 participants

Primary outcome timeframe

Day 21

Results posted on

2024-10-16

Participant Flow

Participant milestones

Participant milestones
Measure	Arm I (Afatinib Dimaleate, Pembrolizumab) DOSE DE-ESCALATION COHORT: Patients receive afatinib dimaleate PO QD on days 1-21 and pembrolizumab IV over 30 minutes on day 1. Courses repeat every 21 days (for up to 2 years for pembrolizumab) in the absence of disease progression or unacceptable toxicity. 6 patients were enrolled into Dose Level 0 at: Afatinib Dimaleate: 40 mg Given PO Pembrolizumab: Given IV No de-escalation was needed prior to expansion.	Arm II (Pembrolizumab, Afatinib Dimaleate) EXPANSION COHORT: Patients receive pembrolizumab IV over 30 minutes on day 1 for 2 courses. Beginning course 3, patients receive afatinib dimaleate PO and pembrolizumab IV as in Arm I. Courses repeat every 21 days (up to 2 years for pembrolizumab) in the absence of disease progression or unacceptable toxicity. All 5 expansion patients were enrolled at Afatinib Dimaleate: 40 mg Given PO Pembrolizumab: Given IV
Overall Study STARTED	6	5
Overall Study COMPLETED	6	5
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pembrolizumab and Afatinib in Patients With Non-small Cell Lung Cancer With Resistance to Erlotinib

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (Afatinib Dimaleate, Pembrolizumab) n=6 Participants DOSE DE-ESCALATION COHORT: Patients receive afatinib dimaleate PO QD on days 1-21 and pembrolizumab IV over 30 minutes on day 1. Courses repeat every 21 days (for up to 2 years for pembrolizumab) in the absence of disease progression or unacceptable toxicity. Afatinib Dimaleate: Given PO Pembrolizumab: Given IV	Arm II (Pembrolizumab, Afatinib Dimaleate) n=5 Participants EXPANSION COHORT: Patients receive pembrolizumab IV over 30 minutes on day 1 for 2 courses. Beginning course 3, patients receive afatinib dimaleate PO and pembrolizumab IV as in Arm I. Courses repeat every 21 days (up to 2 years for pembrolizumab) in the absence of disease progression or unacceptable toxicity. Afatinib Dimaleate: Given PO Pembrolizumab: Given IV	Total n=11 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
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 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
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants	5 participants n=7 Participants	11 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 21

MTD is defined as the dose were less than two patients experienced a dose limiting toxicity. Dose limiting toxicities are defined in the protocol and graded per CTCAE 4.0.

Outcome measures

Outcome measures
Measure	Arm I (Afatinib Dimaleate, Pembrolizumab) n=6 Participants DOSE DE-ESCALATION COHORT: Patients receive afatinib dimaleate PO QD on days 1-21 and pembrolizumab IV over 30 minutes on day 1. Courses repeat every 21 days (for up to 2 years for pembrolizumab) in the absence of disease progression or unacceptable toxicity. Afatinib Dimaleate: Given PO Pembrolizumab: Given IV	Arm II (Pembrolizumab, Afatinib Dimaleate) EXPANSION COHORT: Patients receive pembrolizumab IV over 30 minutes on day 1 for 2 courses. Beginning course 3, patients receive afatinib dimaleate PO and pembrolizumab IV as in Arm I. Courses repeat every 21 days (up to 2 years for pembrolizumab) in the absence of disease progression or unacceptable toxicity. Afatinib Dimaleate: Given PO Pembrolizumab: Given IV	ALL Participants All participants who received protocol treatment of pembrolizumab and afitinib dimaleate.
Maximum Tolerated Dose (MTD) Recommended Dose of Pembrolizumab in Combination With Lead in Pembrolizumab and Afatinib Dimaleate	40 mg	—	—

SECONDARY outcome

Timeframe: Up to 3 years

Population: One patient came off treatment prior to response scan and was not evaluated.

Response classified per RECIST version 1.1 and assessed by CT or MRI: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions; Overall Response (OR) is the best response recorded from the start of the treatment until disease progression/recurrence.

Outcome measures

Outcome measures
Measure	Arm I (Afatinib Dimaleate, Pembrolizumab) n=6 Participants DOSE DE-ESCALATION COHORT: Patients receive afatinib dimaleate PO QD on days 1-21 and pembrolizumab IV over 30 minutes on day 1. Courses repeat every 21 days (for up to 2 years for pembrolizumab) in the absence of disease progression or unacceptable toxicity. Afatinib Dimaleate: Given PO Pembrolizumab: Given IV	Arm II (Pembrolizumab, Afatinib Dimaleate) n=4 Participants EXPANSION COHORT: Patients receive pembrolizumab IV over 30 minutes on day 1 for 2 courses. Beginning course 3, patients receive afatinib dimaleate PO and pembrolizumab IV as in Arm I. Courses repeat every 21 days (up to 2 years for pembrolizumab) in the absence of disease progression or unacceptable toxicity. Afatinib Dimaleate: Given PO Pembrolizumab: Given IV	ALL Participants All participants who received protocol treatment of pembrolizumab and afitinib dimaleate.
Overall Response Rate Per RECIST 1.1	17 percentage of participants	25 percentage of participants	—

SECONDARY outcome

Timeframe: Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 3 years

Population: All ten patients were analyzed together and not broken out by Arm. Numbers by arms reported above, however, overall PFS was: 81 days; 95% CI (8,186)

Outcome measures

Outcome measures
Measure	Arm I (Afatinib Dimaleate, Pembrolizumab) n=6 Participants DOSE DE-ESCALATION COHORT: Patients receive afatinib dimaleate PO QD on days 1-21 and pembrolizumab IV over 30 minutes on day 1. Courses repeat every 21 days (for up to 2 years for pembrolizumab) in the absence of disease progression or unacceptable toxicity. Afatinib Dimaleate: Given PO Pembrolizumab: Given IV	Arm II (Pembrolizumab, Afatinib Dimaleate) n=4 Participants EXPANSION COHORT: Patients receive pembrolizumab IV over 30 minutes on day 1 for 2 courses. Beginning course 3, patients receive afatinib dimaleate PO and pembrolizumab IV as in Arm I. Courses repeat every 21 days (up to 2 years for pembrolizumab) in the absence of disease progression or unacceptable toxicity. Afatinib Dimaleate: Given PO Pembrolizumab: Given IV	ALL Participants n=10 Participants All participants who received protocol treatment of pembrolizumab and afitinib dimaleate.
Progression Free Survival	179 days Interval 27.0 to 510.0	42 days Interval 7.0 to 186.0	81 days Interval 8.0 to 186.0

Adverse Events

Arm I (Afatinib Dimaleate, Pembrolizumab)

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Arm II (Pembrolizumab, Afatinib Dimaleate)

Serious events: 2 serious events

Other events: 5 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Arm I (Afatinib Dimaleate, Pembrolizumab) n=6 participants at risk DOSE DE-ESCALATION COHORT: Patients receive afatinib dimaleate PO QD on days 1-21 and pembrolizumab IV over 30 minutes on day 1. Courses repeat every 21 days (for up to 2 years for pembrolizumab) in the absence of disease progression or unacceptable toxicity. Afatinib Dimaleate: Given PO Pembrolizumab: Given IV	Arm II (Pembrolizumab, Afatinib Dimaleate) n=5 participants at risk EXPANSION COHORT: Patients receive pembrolizumab IV over 30 minutes on day 1 for 2 courses. Beginning course 3, patients receive afatinib dimaleate PO and pembrolizumab IV as in Arm I. Courses repeat every 21 days (up to 2 years for pembrolizumab) in the absence of disease progression or unacceptable toxicity. Afatinib Dimaleate: Given PO Pembrolizumab: Given IV
Gastrointestinal disorders Colitis	0.00% 0/6 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0	20.0% 1/5 • Number of events 1 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0
Infections and infestations Sepsis	0.00% 0/6 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0	20.0% 1/5 • Number of events 1 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0

Other adverse events

Additional Information

Leslie Garcia, Data Research Supervisor

UC Davis Comprehensive Cancer Center

Phone: 916-734-0156

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Arm I (Afatinib Dimaleate, Pembrolizumab) n=6 participants at risk DOSE DE-ESCALATION COHORT: Patients receive afatinib dimaleate PO QD on days 1-21 and pembrolizumab IV over 30 minutes on day 1. Courses repeat every 21 days (for up to 2 years for pembrolizumab) in the absence of disease progression or unacceptable toxicity. Afatinib Dimaleate: Given PO Pembrolizumab: Given IV	Arm II (Pembrolizumab, Afatinib Dimaleate) n=5 participants at risk EXPANSION COHORT: Patients receive pembrolizumab IV over 30 minutes on day 1 for 2 courses. Beginning course 3, patients receive afatinib dimaleate PO and pembrolizumab IV as in Arm I. Courses repeat every 21 days (up to 2 years for pembrolizumab) in the absence of disease progression or unacceptable toxicity. Afatinib Dimaleate: Given PO Pembrolizumab: Given IV
Gastrointestinal disorders Diarrhea	83.3% 5/6 • Number of events 17 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0	80.0% 4/5 • Number of events 6 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0
Skin and subcutaneous tissue disorders Lymphocyte count decreased	16.7% 1/6 • Number of events 1 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0	0.00% 0/5 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0
Metabolism and nutrition disorders Anorexia	0.00% 0/6 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0	20.0% 1/5 • Number of events 1 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0
Metabolism and nutrition disorders Hypokalemia	33.3% 2/6 • Number of events 5 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0	40.0% 2/5 • Number of events 2 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0
Skin and subcutaneous tissue disorders Rash Acneiform	50.0% 3/6 • Number of events 7 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0	60.0% 3/5 • Number of events 3 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0
Investigations Lymphocyte count decreased	66.7% 4/6 • Number of events 6 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0	20.0% 1/5 • Number of events 1 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0
General disorders Anorexia	66.7% 4/6 • Number of events 5 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0	60.0% 3/5 • Number of events 5 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0
General disorders Fatigue	66.7% 4/6 • Number of events 6 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0	40.0% 2/5 • Number of events 3 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0
Investigations Creatinine increased	50.0% 3/6 • Number of events 5 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0	20.0% 1/5 • Number of events 1 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0
Investigations Anemia	83.3% 5/6 • Number of events 8 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0	60.0% 3/5 • Number of events 3 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0
Gastrointestinal disorders Nausea	66.7% 4/6 • Number of events 6 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0	100.0% 5/5 • Number of events 6 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0
Metabolism and nutrition disorders Hypoalbuminemia	50.0% 3/6 • Number of events 5 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0	20.0% 1/5 • Number of events 1 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0
General disorders Weight loss	50.0% 3/6 • Number of events 3 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0	0.00% 0/5 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0
Skin and subcutaneous tissue disorders Dry skin	50.0% 3/6 • Number of events 3 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0	20.0% 1/5 • Number of events 1 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0
Gastrointestinal disorders Colitis	0.00% 0/6 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0	40.0% 2/5 • Number of events 3 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0
Skin and subcutaneous tissue disorders Paronychia	33.3% 2/6 • Number of events 2 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0	0.00% 0/5 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0
Nervous system disorders Headache	33.3% 2/6 • Number of events 2 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0	0.00% 0/5 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0
Gastrointestinal disorders Mucositis oral	16.7% 1/6 • Number of events 2 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0	0.00% 0/5 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0
Skin and subcutaneous tissue disorders Pruritis	16.7% 1/6 • Number of events 2 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0	20.0% 1/5 • Number of events 1 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0
Investigations Elevated Liver Function tests	16.7% 1/6 • Number of events 2 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0	40.0% 2/5 • Number of events 4 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0
Gastrointestinal disorders Vomiting	33.3% 2/6 • Number of events 6 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0	40.0% 2/5 • Number of events 3 • Adverse event data was captured over a period of approximately 2.5 years. CTCAE 4.0