AMG 102 and Erlotinib for Advanced Non-Small Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT01233687
• Recruitment Status: Completed
• First Posted: November 3, 2010
• Results First Posted: September 1, 2016
• Last Update Posted: June 22, 2017
• Sponsor: Ahmad Tarhini
• Collaborator: Amgen
• Information provided by (Responsible Party): Ahmad Tarhini, University of Pittsburgh

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Carcinoma, Non-Small-Cell Lung
• Intervention: Drug: AMG 102 and erlotinib
• Enrollment: 49

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	AMG 102 + Erlotinib
Arm/Group Description	[Not Specified]
Period Title: Phase I RP2D AMG 102 + Erlotinib
Started	7
Completed	7
Not Completed	0
Period Title: Phase II AMG 102 + Erlotinib
Started	49 [1]
Response-Evaluable	45
Completed	45
Not Completed	4
Reason Not Completed
Death	1
Physician Decision	2
Withdrawal by Subject	1
[1] Includes 7 participants from Phase 1 part of study.

Baseline Characteristics

Arm/Group Title		AMG 102 + Erlotinib
Arm/Group Description		[Not Specified]
Overall Number of Baseline Participants		45
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	45 participants
		65; (35 to 82)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	45 participants
	Female	20 44.4%
	Male	25 55.6%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants That Experienced a Dose Limiting Toxicity
Description	Determination of the safety and recommended phase II dose of AMG 102 when combined with erlotinib for the treatment of patients with advanced, previously-treated NSCLC.
Time Frame	During first cycle of treatment (3 weeks)

Outcome Measure Data

Analysis Population Description

In the absence of DLTs among the first 7 pts treated, AMG 102 + Erlotinib (150 mg) daily (3 weeks) was declared the RP2D.

Arm/Group Title	AMG 102 + Erlotinib
Arm/Group Description:	[Not Specified]
Overall Number of Participants Analyzed	7
Measure Type: Number; Number (90% Confidence Interval); Unit of Measure: percentage of participants
	0; (0 to 0)

2. Primary Outcome

Title	Disease Control Rate (DCR)
Description	Using RECIST v1.1 criteria, DCR was determined by following equation: the number of complete response (CR) participants + the number of partial response (PR) participants + the number of stable disease (SD) participants / the number of complete response (CR) participants + the number of partial response (PR) participants + the number of stable disease (SD) participants + the number of progressive disease (PD) participants.
Time Frame	Six weeks from initiation of treatment with AMG 102 + Erlotinib

Outcome Measure Data

Analysis Population Description

All patients who who received at least one dose of AMG 102 and had post-treatment imaging studies for response evaluation using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria at six weeks (RESPONSE EVALUABLE)

Arm/Group Title	AMG 102 + Erlotinib
Arm/Group Description:	[Not Specified]
Overall Number of Participants Analyzed	45
Measure Type: Number; Number (90% Confidence Interval); Unit of Measure: percentage of patients
	60; (47 to 71)

3. Secondary Outcome

Title	Objective Response Rate (ORR/Clinical Response)
Description	Using RECIST v1.1 criteria, ORR was determined by following equation: the number of partial response (PR) participants / the number of partial response (PR) participants + the number of stable disease (SD) participants + the number of progressive disease (PD) participants.
Time Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

All patients who who received at least one dose of AMG 102 and had post-treatment imaging studies for response evaluation using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria at six weeks (RESPONSE EVALUABLE)

Arm/Group Title	AMG 102 + Erlotinib
Arm/Group Description:	[Not Specified]
Overall Number of Participants Analyzed	45
Measure Type: Number; Number (90% Confidence Interval); Unit of Measure: percentage of patients
	8.8; (0.4 to 18.4)

4. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	Progression-free survival is defined as the time from the start of treatment until first evidence of disease progression, death, or date of last contact. The (median) length of time that subjects with previously-treated advanced NSCLC, who were treated with the combination of AMG 102 and erlotinib, are both alive and free of disease progression as estimated by the Kaplan-Meier method. For participants not known to have died as of the data cut-off date and who did not have PD, the PFS date was censored at the last contact date (contacts considered in the determination of last progression free disease assessment).
Time Frame	Up to 24 months (after the first patient is accrued)

Outcome Measure Data

Analysis Population Description

All patients who who received at least one dose of AMG 102 and had post-treatment imaging studies for response evaluation using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria at six weeks (RESPONSE EVALUABLE)

Arm/Group Title	AMG 102 + Erlotinib
Arm/Group Description:	[Not Specified]
Overall Number of Participants Analyzed	45
Median (90% Confidence Interval); Unit of Measure: months
	2.6; (1.4 to 3.3)

5. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall Survival was computed for all participants and is defined as the time between start of treatment and death. The (median) length of time in months that subjects with previously-treated advanced NSCLC, treated with the combination of AMG 102 and erlotinib, remain alive estimated by the Kaplan-Meier method.
Time Frame	Up to 24 months (after the first evaluable patient is accrued)

Outcome Measure Data

Analysis Population Description

All patients who who received at least one dose of AMG 102 and had post-treatment imaging studies for response evaluation using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria at six weeks (RESPONSE EVALUABLE)

Arm/Group Title	AMG 102 + Erlotinib
Arm/Group Description:	[Not Specified]
Overall Number of Participants Analyzed	45
Median (90% Confidence Interval); Unit of Measure: months
	6.6; (5.6 to 8.9)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	AMG 102 + Erlotinib
Arm/Group Description	Serious and Non-Serious Adverse Events include the events considered at least possibly, probably or definitely related to study treatment. Non-Serious (Other) Adverse Events include those that occurred with a frequency of more than or equal to 5%.
All-Cause Mortality
	AMG 102 + Erlotinib
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	AMG 102 + Erlotinib
	Affected / at Risk (%)
Total	18/45 (40.00%)
Blood and lymphatic system disorders
Anemia †	1/45 (2.22%)
Gastrointestinal disorders
Diarrhea †	1/45 (2.22%)
Mucositis oral †	1/45 (2.22%)
Nausea †	1/45 (2.22%)
Vomiting †	1/45 (2.22%)
General disorders
Edema limbs †	1/45 (2.22%)
Infections and infestations
Infections and infestations - Other, specify †	1/45 (2.22%)
Nervous system disorders
Syncope †	1/45 (2.22%)
Respiratory, thoracic and mediastinal disorders
Dyspnea †	5/45 (11.11%)
Skin and subcutaneous tissue disorders
Rash acneiform †	1/45 (2.22%)
Vascular disorders
Thromboembolic event †	4/45 (8.89%)
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	AMG 102 + Erlotinib
	Affected / at Risk (%)
Total	45/45 (100.00%)
Blood and lymphatic system disorders
Blood and lymphatic system disorders	4/45 (8.89%)
Anemia	21/45 (46.67%)
Gastrointestinal disorders
Vomiting	8/45 (17.78%)
Nausea	16/45 (35.56%)
Diarrhea	24/45 (53.33%)
General disorders
Edema limbs	8/45 (17.78%)
Fatigue	18/45 (40.00%)
Investigations
Platelet count decreased	5/45 (11.11%)
Alanine aminotransferase increased	7/45 (15.56%)
Creatinine increased	7/45 (15.56%)
Blood bilirubin increased	8/45 (17.78%)
Aspartate aminotransferase increased	10/45 (22.22%)
Lymphocyte count decreased	15/45 (33.33%)
Alkaline phosphatase increased	16/45 (35.56%)
Metabolism and nutrition disorders
Anorexia	13/45 (28.89%)
Hypomagnesemia	20/45 (44.44%)
Nervous system disorders
Peripheral sensory neuropathy	3/45 (6.67%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	8/45 (17.78%)
Cough	10/45 (22.22%)
Skin and subcutaneous tissue disorders
Alopecia	4/45 (8.89%)
Rash maculo-papular	4/45 (8.89%)
Pruritus	5/45 (11.11%)
Skin and subcutaneous tissue disorders - Other, specify	9/45 (20.00%)
Rash acneiform	30/45 (66.67%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Ahmad Tarhini, MD
• Organization: University of Pittsburgh
• Phone: (412) 648-6578
• EMail: tarhiniaa@upmc.edu

• Responsible Party: Ahmad Tarhini, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT01233687
• Other Study ID Numbers: 10-058
• First Submitted: November 2, 2010
• First Posted: November 3, 2010
• Results First Submitted: January 12, 2016
• Results First Posted: September 1, 2016
• Last Update Posted: June 22, 2017