Trial Outcomes & Findings for A Phase 1/2 Trial of Trametinib and Erlotinib in Patients With EGFR-Mutant Lung Adenocarcinomas and Acquired Resistance to Erlotinib (NCT NCT03076164)

Last Updated: 2024-04-02

Results Overview

Response and progression of disease will be evaluated in this study using interval imaging every 8 weeks with CT scan of the chest and imaging of any other target lesion with response evaluated by RECIST 1.1.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

24 participants

Primary outcome timeframe

2 years

Results posted on

2024-04-02

Participant Flow

This treatment regimen was already assessed in a previous study. The phase 1 portion was a safety lead-in of a slight modification of the previously established combination dosing. As a consequence, we only did a safety lead in of one dose level that was determined to be the phase 2 dose and we rolled all the phase 1 patients into the phase 2 cohort.

Participant milestones

Participant milestones
Measure	Trametinib 1.5mg + Erlotinib 75mg Phase 1: Accrue 6 patients on Trametinib 1.5mg + Erlotinib 75mg by mouth once daily Phase 2: Accrue 24 patients (including 6 patients treated during Phase 1) daily doses of 75mg erlotinib and 1.5mg trametinib This treatment regimen was already assessed in a previous study. The phase 1 portion was a safety lead-in of a slight modification of the previously established combination dosing. As a consequence, we only did a safety lead in of one dose level that was determined to be the phase 2 dose and we rolled all the phase 1 patients into the phase 2 cohort. There would be no reason or utility to assess the phase 1 cohort separately since they received the same dose as the phase 2 cohort.
Overall Study STARTED	24
Overall Study COMPLETED	24
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Phase 1/2 Trial of Trametinib and Erlotinib in Patients With EGFR-Mutant Lung Adenocarcinomas and Acquired Resistance to Erlotinib

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Trametinib 1.5mg + Erlotinib 75mg n=24 Participants Phase 1: Accrue 6 patients on Trametinib 1.5mg + Erlotinib 75mg by mouth once daily Phase 2: Accrue 24 patients (including 6 patients treated during Phase 1) daily doses of 75mg erlotinib and 1.5mg trametinib This treatment regimen was already assessed in a previous study. The phase 1 portion was a safety lead-in of a slight modification of the previously established combination dosing. As a consequence, we only did a safety lead in of one dose level that was determined to be the phase 2 dose and we rolled all the phase 1 patients into the phase 2 cohort.
Age, Continuous	62 years n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	8 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants
Region of Enrollment United States	24 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 years

Outcome measures

Outcome measures
Measure	Trametinib 1.5mg + Erlotinib 75mg n=24 Participants Phase 1: Accrue 6 patients on Trametinib 1.5mg + Erlotinib 75mg by mouth once daily Phase 2: Accrue 24 patients (including 6 patients treated during Phase 1) daily doses of 75mg erlotinib and 1.5mg trametinib This treatment regimen was already assessed in a previous study. The phase 1 portion was a safety lead-in of a slight modification of the previously established combination dosing. As a consequence, we only did a safety lead in of one dose level that was determined to be the phase 2 dose and we rolled all the phase 1 patients into the phase 2 cohort. There would be no reason or utility to assess the phase 1 cohort separately since they received the same dose as the phase 2 cohort.
Participants Response Rate Stable Disease	11 participants
Participants Response Rate Progression of disease	4 participants
Participants Response Rate Not Entered	8 participants
Participants Response Rate Partial Response	1 participants

PRIMARY outcome

Timeframe: 2 years

Safety and tolerability will be evaluated by systematic and regular toxicity evaluations. Toxicity will be graded according to NCI CTCAE version 4.0.

Outcome measures

Outcome measures
Measure	Trametinib 1.5mg + Erlotinib 75mg n=24 Participants Phase 1: Accrue 6 patients on Trametinib 1.5mg + Erlotinib 75mg by mouth once daily Phase 2: Accrue 24 patients (including 6 patients treated during Phase 1) daily doses of 75mg erlotinib and 1.5mg trametinib This treatment regimen was already assessed in a previous study. The phase 1 portion was a safety lead-in of a slight modification of the previously established combination dosing. As a consequence, we only did a safety lead in of one dose level that was determined to be the phase 2 dose and we rolled all the phase 1 patients into the phase 2 cohort. There would be no reason or utility to assess the phase 1 cohort separately since they received the same dose as the phase 2 cohort.
Number of Participants Evaluated for Toxicities	24 Participants

Adverse Events

Trametinib 1.5mg + Erlotinib 75mg

Serious events: 6 serious events

Other events: 24 other events

Deaths: 20 deaths

Serious adverse events

Serious adverse events
Measure	Trametinib 1.5mg + Erlotinib 75mg n=24 participants at risk Phase 1: Accrue 6 patients on Trametinib 1.5mg + Erlotinib 75mg by mouth once daily Phase 2: Accrue 24 patients (including 6 patients treated during Phase 1) daily doses of 75mg erlotinib and 1.5mg trametinib This treatment regimen was already assessed in a previous study. The phase 1 portion was a safety lead-in of a slight modification of the previously established combination dosing. As a consequence, we only did a safety lead in of one dose level that was determined to be the phase 2 dose and we rolled all the phase 1 patients into the phase 2 cohort.
Blood and lymphatic system disorders Anemia	4.2% 1/24 • 2 years
Cardiac disorders Cardiac arrest	4.2% 1/24 • 2 years
Metabolism and nutrition disorders Dehydration	4.2% 1/24 • 2 years
Gastrointestinal disorders Diarrhea	8.3% 2/24 • 2 years
Respiratory, thoracic and mediastinal disorders Dyspnea	16.7% 4/24 • 2 years
General disorders Fatigue	4.2% 1/24 • 2 years
Gastrointestinal disorders Hemorrhoidal hemorrhage	4.2% 1/24 • 2 years
Respiratory, thoracic and mediastinal disorders Hypoxia	4.2% 1/24 • 2 years
General disorders Malaise	4.2% 1/24 • 2 years
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.2% 1/24 • 2 years
Respiratory, thoracic and mediastinal disorders Pneumothorax	4.2% 1/24 • 2 years
Skin and subcutaneous tissue disorders Rash maculo-papular	4.2% 1/24 • 2 years
Infections and infestations Sepsis	4.2% 1/24 • 2 years
Gastrointestinal disorders Vomiting	8.3% 2/24 • 2 years

Other adverse events

Other adverse events
Measure	Trametinib 1.5mg + Erlotinib 75mg n=24 participants at risk Phase 1: Accrue 6 patients on Trametinib 1.5mg + Erlotinib 75mg by mouth once daily Phase 2: Accrue 24 patients (including 6 patients treated during Phase 1) daily doses of 75mg erlotinib and 1.5mg trametinib This treatment regimen was already assessed in a previous study. The phase 1 portion was a safety lead-in of a slight modification of the previously established combination dosing. As a consequence, we only did a safety lead in of one dose level that was determined to be the phase 2 dose and we rolled all the phase 1 patients into the phase 2 cohort.
Gastrointestinal disorders Diarrhea	87.5% 21/24 • 2 years
General disorders Fatigue	62.5% 15/24 • 2 years
Skin and subcutaneous tissue disorders Rash acneiform	54.2% 13/24 • 2 years
Gastrointestinal disorders Nausea	33.3% 8/24 • 2 years
Skin and subcutaneous tissue disorders Rash maculo-papular	33.3% 8/24 • 2 years
Gastrointestinal disorders Vomiting	29.2% 7/24 • 2 years
Investigations Aspartate aminotransferase increased	25.0% 6/24 • 2 years
Skin and subcutaneous tissue disorders Dry skin	25.0% 6/24 • 2 years
Metabolism and nutrition disorders Anorexia	20.8% 5/24 • 2 years
Gastrointestinal disorders Constipation	20.8% 5/24 • 2 years
Respiratory, thoracic and mediastinal disorders Dyspnea	20.8% 5/24 • 2 years
Skin and subcutaneous tissue disorders Pruritus	20.8% 5/24 • 2 years
Investigations Alanine aminotransferase increased	16.7% 4/24 • 2 years
Blood and lymphatic system disorders Anemia	16.7% 4/24 • 2 years
General disorders Edema limbs	16.7% 4/24 • 2 years
Gastrointestinal disorders Gastroesophageal reflux disease	16.7% 4/24 • 2 years
Respiratory, thoracic and mediastinal disorders Cough	12.5% 3/24 • 2 years
General disorders Fever	12.5% 3/24 • 2 years
Gastrointestinal disorders Mucositis oral	12.5% 3/24 • 2 years
Respiratory, thoracic and mediastinal disorders Pleural effusion	12.5% 3/24 • 2 years
Infections and infestations Skin infection	12.5% 3/24 • 2 years
Gastrointestinal disorders Abdominal pain	12.5% 3/24 • 2 years
General disorders Gen disorders & admin site conditions Other, spec	8.3% 2/24 • 2 years
General disorders Malaise	8.3% 2/24 • 2 years
Musculoskeletal and connective tissue disorders Myalgia	8.3% 2/24 • 2 years
Gastrointestinal disorders Rectal hemmorhage	8.3% 2/24 • 2 years
Skin and subcutaneous tissue disorders Skin & subcutaneous tissue disorders Other, spec	8.3% 2/24 • 2 years

Additional Information

Dr. Helene Yu, MD

Memorial Sloan Kettering Cancer Center

Phone: 646-608-3912

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place