Trial Outcomes & Findings for BATTLE-2 Program: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non-Small Cell Lung Cancer (NCT NCT01248247)

Last Updated: 2022-01-12

Results Overview

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

334 participants

Primary outcome timeframe

8 weeks

Results posted on

2022-01-12

Participant Flow

Patients with pretreated NSCLC who agreed to a baseline tumor biopsy, who had ECOG P of 0 to 2, and who had multiple prior lines of therapy and stable or treated brain metastases were enrolled. Patients were excluded if their tumor harbored EGFR sensitizing mutations or ALK gene fusions, and they were erlotinib or crizotinib na¨ıve.

Total of 334 participants consented, 134 participants did not receive treatment a majority due to screen failures and others due to participants withdrew consent(s) and or progressed prior to treatment starting.

Participant milestones

Participant milestones
Measure	Arm 1 - Erlotinib Erlotinib 150 mg by mouth each day of a 28 day cycle.	Arm 2 - Erlotinib + MK-2206 Erlotinib 150 mg by mouth each day of a 28 day cycle. MK-2206 135 mg by mouth every week of a 28 day cycle.	Arm 3 - AZD6244 + MK-2206 AZD6244 100 mg by mouth daily of a 28 day cycle. MK-2206 100 mg by mouth every week of a 28 day cycle.	Arm 4 - Sorafenib Sorafenib 400 mg by mouth twice a day for a 28 day cycle.
Overall Study STARTED	22	42	75	61
Overall Study COMPLETED	0	0	0	0
Overall Study NOT COMPLETED	22	42	75	61

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm 1 - Erlotinib Erlotinib 150 mg by mouth each day of a 28 day cycle.	Arm 2 - Erlotinib + MK-2206 Erlotinib 150 mg by mouth each day of a 28 day cycle. MK-2206 135 mg by mouth every week of a 28 day cycle.	Arm 3 - AZD6244 + MK-2206 AZD6244 100 mg by mouth daily of a 28 day cycle. MK-2206 100 mg by mouth every week of a 28 day cycle.	Arm 4 - Sorafenib Sorafenib 400 mg by mouth twice a day for a 28 day cycle.
Overall Study Adverse Event	2	4	4	2
Overall Study Death	0	1	4	7
Overall Study Lost to Follow-up	0	1	1	0
Overall Study Alternative treatment	0	1	0	0
Overall Study Other	2	8	8	5
Overall Study Progression	18	27	56	44
Overall Study Refuse further treatment	0	0	1	2
Overall Study Complicating disease	0	0	1	1

Baseline Characteristics

BATTLE-2 Program: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1 - Erlotinib n=22 Participants Erlotinib 150 mg by mouth each day of a 28 day cycle.	Arm 2 - Erlotinib + MK-2206 n=42 Participants Erlotinib 150 mg by mouth each day of a 28 day cycle. MK-2206 135 mg by mouth every week of a 28 day cycle.	Arm 3 - AZD6244 + MK-2206 n=75 Participants AZD6244 100 mg by mouth daily of a 28 day cycle. MK-2206 100 mg by mouth every week of a 28 day cycle.	Arm 4 - Sorafenib n=61 Participants Sorafenib 400 mg by mouth twice a day for a 28 day cycle.	Total n=200 Participants Total of all reporting groups
Age, Continuous	61 years n=5 Participants	62 years n=7 Participants	61 years n=5 Participants	62 years n=4 Participants	61 years n=21 Participants
Age, Customized <=49 years	2 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants	7 Participants n=4 Participants	17 Participants n=21 Participants
Age, Customized Between 50 and 59 years	8 Participants n=5 Participants	16 Participants n=7 Participants	27 Participants n=5 Participants	19 Participants n=4 Participants	70 Participants n=21 Participants
Age, Customized Between 60 and 69 years	10 Participants n=5 Participants	12 Participants n=7 Participants	29 Participants n=5 Participants	24 Participants n=4 Participants	75 Participants n=21 Participants
Age, Customized >=70 years	2 Participants n=5 Participants	12 Participants n=7 Participants	13 Participants n=5 Participants	11 Participants n=4 Participants	38 Participants n=21 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	15 Participants n=7 Participants	49 Participants n=5 Participants	32 Participants n=4 Participants	106 Participants n=21 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	27 Participants n=7 Participants	26 Participants n=5 Participants	29 Participants n=4 Participants	94 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants	14 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=5 Participants	41 Participants n=7 Participants	72 Participants n=5 Participants	54 Participants n=4 Participants	186 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	4 Participants n=21 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	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants	8 Participants n=4 Participants	19 Participants n=21 Participants
Race (NIH/OMB) White	18 Participants n=5 Participants	40 Participants n=7 Participants	67 Participants n=5 Participants	51 Participants n=4 Participants	176 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment United States	22 participants n=5 Participants	42 participants n=7 Participants	75 participants n=5 Participants	61 participants n=4 Participants	200 participants n=21 Participants
KRAS mut+ No	16 Participants n=5 Participants	34 Participants n=7 Participants	53 Participants n=5 Participants	43 Participants n=4 Participants	146 Participants n=21 Participants
KRAS mut+ Yes	6 Participants n=5 Participants	8 Participants n=7 Participants	22 Participants n=5 Participants	18 Participants n=4 Participants	54 Participants n=21 Participants

PRIMARY outcome

Timeframe: 8 weeks

Population: 12 participants were inevaluable and 2 participants were not applicable.

Outcome measures

Outcome measures
Measure	Arm 1 - Erlotinib n=19 Participants Erlotinib 150 mg by mouth each day of a 28 day cycle.	Arm 2 - Erlotinib + MK-2206 n=36 Participants Erlotinib 150 mg by mouth each day of a 28 day cycle. MK-2206 135 mg by mouth every week of a 28 day cycle.	Arm 3 - AZD6244 + MK-2206 n=70 Participants AZD6244 100 mg by mouth daily of a 28 day cycle. MK-2206 100 mg by mouth every week of a 28 day cycle.	Arm 4 - Sorafenib n=61 Participants Sorafenib 400 mg by mouth twice a day for a 28 day cycle.
8-Week Disease Control Rate (DCR) Partial Response	0 Participants	0 Participants	3 Participants	3 Participants
8-Week Disease Control Rate (DCR) Stable Disease	6 Participants	18 Participants	34 Participants	25 Participants
8-Week Disease Control Rate (DCR) Progressive Disease	13 Participants	18 Participants	33 Participants	33 Participants

SECONDARY outcome

Timeframe: From the date of drug start to the earliest sign of disease progression or death

Progression-free survival was estimated by Kaplan-Meier method

Outcome measures

Outcome measures
Measure	Arm 1 - Erlotinib n=22 Participants Erlotinib 150 mg by mouth each day of a 28 day cycle.	Arm 2 - Erlotinib + MK-2206 n=42 Participants Erlotinib 150 mg by mouth each day of a 28 day cycle. MK-2206 135 mg by mouth every week of a 28 day cycle.	Arm 3 - AZD6244 + MK-2206 n=75 Participants AZD6244 100 mg by mouth daily of a 28 day cycle. MK-2206 100 mg by mouth every week of a 28 day cycle.	Arm 4 - Sorafenib n=61 Participants Sorafenib 400 mg by mouth twice a day for a 28 day cycle.
Median Progression-free Survival	1.8 months Interval 1.6 to 3.5	2.5 months Interval 1.9 to 3.5	2.2 months Interval 1.8 to 3.6	2.1 months Interval 1.8 to 2.8

Adverse Events

Arm 1 - Erlotinib

Serious events: 3 serious events

Other events: 21 other events

Deaths: 19 deaths

Arm 2 - Erlotinib + MK-2206

Serious events: 13 serious events

Other events: 42 other events

Deaths: 36 deaths

Arm 3 - AZD6244 + MK-2206

Serious events: 29 serious events

Other events: 75 other events

Deaths: 65 deaths

Arm 4 - Sorafenib

Serious events: 24 serious events

Other events: 61 other events

Deaths: 51 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Marcelo Vailati Negrao, MD, Assistant Professor, Thoracic-Head & Neck Med Onc

UT MD Anderson Cancer Center

Phone: (713) 614-4938

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Arm 1 - Erlotinib n=22 participants at risk Erlotinib 150 mg by mouth each day of a 28 day cycle.	Arm 2 - Erlotinib + MK-2206 n=42 participants at risk Erlotinib 150 mg by mouth each day of a 28 day cycle. MK-2206 135 mg by mouth every week of a 28 day cycle.	Arm 3 - AZD6244 + MK-2206 n=75 participants at risk AZD6244 100 mg by mouth daily of a 28 day cycle. MK-2206 100 mg by mouth every week of a 28 day cycle.	Arm 4 - Sorafenib n=61 participants at risk Sorafenib 400 mg by mouth twice a day for a 28 day cycle.
General disorders Fatigue	9.1% 2/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	35.7% 15/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	41.3% 31/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	42.6% 26/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Gastrointestinal disorders Diarrhea	36.4% 8/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	57.1% 24/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	34.7% 26/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	26.2% 16/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Skin and subcutaneous tissue disorders Rash Maculopapular	13.6% 3/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	33.3% 14/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	38.7% 29/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	39.3% 24/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Skin and subcutaneous tissue disorders Rash Acneiform	50.0% 11/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	42.9% 18/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	38.7% 29/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	4.9% 3/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Gastrointestinal disorders Nausea	31.8% 7/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	31.0% 13/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	33.3% 25/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	19.7% 12/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Gastrointestinal disorders Vomiting	22.7% 5/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	23.8% 10/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	36.0% 27/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	23.0% 14/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Skin and subcutaneous tissue disorders Dry skin	31.8% 7/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	28.6% 12/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	17.3% 13/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	29.5% 18/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Metabolism and nutrition disorders Anorexia	27.3% 6/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	38.1% 16/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	12.0% 9/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	24.6% 15/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Investigations Increased AST	22.7% 5/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	11.9% 5/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	38.7% 29/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	11.5% 7/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Metabolism and nutrition disorders Hyperglycemia	9.1% 2/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	26.2% 11/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	32.0% 24/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	6.6% 4/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Gastrointestinal disorders Oral mucositis	13.6% 3/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	31.0% 13/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	18.7% 14/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	16.4% 10/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Investigations Increased alkaline phosphatase	9.1% 2/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	23.8% 10/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	22.7% 17/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	36.1% 22/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Investigations Weight loss	13.6% 3/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	26.2% 11/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	2.7% 2/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	8.2% 5/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Investigations Increased ALT	0.00% 0/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	11.9% 5/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	29.3% 22/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	14.8% 9/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Skin and subcutaneous tissue disorders Pruritus	4.5% 1/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	9.5% 4/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	10.7% 8/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	8.2% 5/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Skin and subcutaneous tissue disorders Other skin and subcutaneous tissue disorders, specify	13.6% 3/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	7.1% 3/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	10.7% 8/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	11.5% 7/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Respiratory, thoracic and mediastinal disorders Dyspnea	4.5% 1/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	4.8% 2/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	10.7% 8/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	24.6% 15/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	4.5% 1/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	0.00% 0/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	1.3% 1/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	4.9% 3/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Gastrointestinal disorders Dry mouth	4.5% 1/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	14.3% 6/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	8.0% 6/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	8.2% 5/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Investigations Increased blood bilirubin	22.7% 5/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	4.8% 2/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	1.3% 1/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	14.8% 9/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Metabolism and nutrition disorders Hyponatremia	4.5% 1/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	7.1% 3/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	0.00% 0/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	11.5% 7/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	2.4% 1/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	6.7% 5/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	16.4% 10/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Vascular disorders Hypertension	0.00% 0/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	2.4% 1/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	2.7% 2/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	11.5% 7/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Blood and lymphatic system disorders Anemia	0.00% 0/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	4.8% 2/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	2.7% 2/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	11.5% 7/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Metabolism and nutrition disorders Hypoalbuminemia	4.5% 1/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	2.4% 1/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	1.3% 1/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	0.00% 0/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Nervous system disorders Dysgeusia	4.5% 1/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	11.9% 5/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	4.0% 3/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	3.3% 2/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Investigations Increased creatinine	0.00% 0/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	11.9% 5/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	2.7% 2/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	13.1% 8/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Respiratory, thoracic and mediastinal disorders Hoarseness	0.00% 0/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	0.00% 0/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	1.3% 1/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	6.6% 4/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Respiratory, thoracic and mediastinal disorders Epistaxis	13.6% 3/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	0.00% 0/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	1.3% 1/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	13.1% 8/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/22 • From the first dose through 30 days after the last dose of study medication, up to 3 years	0.00% 0/42 • From the first dose through 30 days after the last dose of study medication, up to 3 years	0.00% 0/75 • From the first dose through 30 days after the last dose of study medication, up to 3 years	6.6% 4/61 • From the first dose through 30 days after the last dose of study medication, up to 3 years