A Study of MM-121 Combination Therapy in Patients With Advanced Non-Small Cell Lung Cancer

• Sponsor: Merrimack Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00994123
• Collaborator: (none)
• Enrollment: 162
• Locations: 38
• Arms: 3
• Duration (Months): 63.9
• Patients Per Site: 4.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

A Phase 1-2 study of MM-121 in combination with standard therapy for non-small cell lung cancer (NSCLC).

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Non-Small-Cell Lung	Drug: MM-121; Drug: Erlotinib	Phase 1/Phase 2

Detailed Description

Phase 1: Patients with Non-Small Cell Lung Cancer (NSCLC) may be enrolled to evaluate the safety, tolerability and recommended Phase 2 dose of MM-121 in combination with standard therapy.

Phase 2: Patients with Non-Small Cell Lung Cancer (NSCLC) may be enrolled to estimate the progression-free survival of the MM-121 + standard therapy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 162 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1-2 Trial of MM-121 in Combination With Erlotinib in Three Groups of Patients With Non-Small Cell Lung Cancer
• Study Start Date: Feb 1, 2010
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1: Dose-Escalation Escalating doses of MM-121 (QOW IV) and erlotinib (daily PO)	Drug: MM-121; MM-121 (SAR256212) = intravenous solution; Other Names: SAR256212 ; Drug: Erlotinib; erlotinib = daily oral tablet; Other Names: Tarceva
Active Comparator: Phase 2: Control Erlotinib (daily)	Drug: Erlotinib; erlotinib = daily oral tablet; Other Names: Tarceva
Experimental: Phase 2: Treatment MM-121 (QOW IV) and erlotinib (daily PO)	Drug: MM-121; MM-121 (SAR256212) = intravenous solution; Other Names: SAR256212 ; Drug: Erlotinib; erlotinib = daily oral tablet; Other Names: Tarceva

Outcome Measures

Primary Outcome Measures

1. Phase 1: To Determine the Recommended Phase 2 Dose of the MM-121 + Erlotinib Combination Based Upon Either the Maximum Tolerated Dose (MTD) or the Maximum Feasible Dose of the Combination in Patients With NSCLC. [From date of first dose to 30 days after termination, the longest 175 weeks]

   To establish the safety of escalating doses of MM-121 in combination with erlotinib in order to determine the recommended phase 2 dose of the combination for the second part of the study. Dose-escalation conducted using standard 3+3 model to determine maximum tolerated dose. Reports of Dose-Limiting Toxicities (DLTs) were assessed to determine the MTD.

2. Phase 1: Determine the Maximum Tolerated Dose Dependent on Reports of Dose-limiting Toxicities [From date of first dose to 30 days after termination, the longest 175 weeks]

   Using a 3+3 dose escalation model, the maximum tolerated dose was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in the expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was used as the recommended Phase 2 dose.

3. Phase 2: Progression-free Survival of the MM-121 + Erlotinib Combination [Time from first dose to date of progression, with a median of 8.1 weeks]

   This was a time-to-event measure using Progression-Free Survival (PFS) comparing MM-121 + erlotinib vs.erlotinib alone. Progression of disease is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions". Progression free survival was defined as the number of weeks from the date of randomization to the date of death or progression. If neither death nor progression was observed during the study, PFS data was censored at the last non-progressive disease valid tumor assessment unless the patient was discontinued due to symptomatic deterioration. If this occurred, the patient was counted as having progressive disease (PD).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with locally advanced or metastatic non-small cell lung cancer.

• Patients must be >/= 18 years of age.

• Patients must have adequate Performance Status (PS) as measured by ECOG and adequate end organ function.

Exclusion Criteria:

• Patients with a recent history (within 5 years) of another malignancy.

• Patients who are pregnant or nursing.

• Patients with clinically significant heart failure.

• Patients with clinically significant eye or gastrointestinal abnormalities.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States	35294
2		Tucson	Arizona	United States	85715
3		Loma Linda	California	United States	92354
4		Sacramento	California	United States	95817
5		San Francisco	California	United States	94115
6		Aurora	Colorado	United States	80045
7		Tampa	Florida	United States	33612
8		Atlanta	Georgia	United States	30322
9		Lafayette	Indiana	United States	47905
10		Boston	Massachusetts	United States	02114
11		St. Louis	Missouri	United States	63110
12		Buffalo	New York	United States	14263
13		New York	New York	United States	10065
14		Cincinnati	Ohio	United States	45267
15		Portland	Oregon	United States	97239
16		Pittsburgh	Pennsylvania	United States	15232
17		Charleston	South Carolina	United States	29425
18		Nashville	Tennessee	United States	37232
19		Dallas	Texas	United States	75390
20		Edmonton	Alberta	Canada
21		Toronto	Ontario	Canada	M5G2M9
22		Montreal	Quebec	Canada
23		Heidelberg	Mannheim	Germany	68167
24		Bad Berka		Germany	99437
25		Frankfurt		Germany	60488
26		Heidelberg		Germany	69126
27		Lungenklinik		Germany
28		Ulm		Germany	89081
29		Seoul	Gangnam-gu	Korea, Republic of	135-710
30		Seoul	Seodaemun-gu	Korea, Republic of	120-752
31		Barcelona		Spain	08035
32		Madrid		Spain
33		Malaga		Spain	29010
34		Guishan	Taoyuan County	Taiwan	33305
35		Taichung		Taiwan	40705
36		Taichung		Taiwan
37		Tainan City		Taiwan	70146
38		Taipei		Taiwan	100

Sponsors and Collaborators

• Merrimack Pharmaceuticals

Investigators

• Study Director: Victor Moyo, MD, Merrimack Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merrimack Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00994123
• Other Study ID Numbers: MM-121-01-101
• First Posted: Oct 14, 2009
• Last Update Posted: Aug 22, 2016
• Last Verified: Jul 1, 2016

• Keywords provided by Merrimack Pharmaceuticals: Non-Small Cell Lung Cancer; NSCLC; Advanced Non-Small Cell Lung Cancer; Metastatic Non-Small Cell Lung Cancer; Lung Cancer; Erlotinib; Tarceva; MM-121; ErbB3; Her3; Epidermal Growth Factor Receptor; anti-ErbB3 human monoclonal antibody; ErbB3 antagonist
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Erlotinib Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Phase 1: MM-121 + Erlotinib	Phase 2: MM-121 + Erlotinib	Phase 2: Erlotinib
Arm/Group Description	Escalating doses of MM-121 and erlotinib	EGFR wild-type, EGFR-TKI naive patients randomized to receive: MM-121 every other week at a dose of 20 mg/kg IV in combination with daily 100 mg erlotinib p.o.	EGFR wild-type, EGFR-TKI naive patients randomized to receive: daily 150 mg erlotinib p.o. alone
Period Title: Overall Study
STARTED	33	85	44
COMPLETED	33	85	44
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Phase 1: MM-121 + Erlotinib	Phase 2: MM-121 + Erlotinib	Phase 2: Erlotinib	Total
Arm/Group Description	Escalating doses of MM-121 + Erlotinib in patients with NSCLC	EGFR wild-type, EGFR-TKI naive patients randomized to receive: MM-121 every other week at a dose of 20 mg/kg IV in combination with daily 100 mg erlotinib p.o.	EGFR wild-type, EGFR-TKI naive patients randomized to receive: daily 150 mg erlotinib p.o. alone	Total of all reporting groups
Overall Participants	33	85	44	162
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.5 (10.12)	62.9 (10.74)	63.9 (10.16)	63.2 (10.53)
Sex: Female, Male (Count of Participants)
Female	17 51.5%	35 41.2%	17 38.6%	69 42.6%
Male	16 48.5%	50 58.8%	27 61.4%	93 57.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 6.1%	3 3.5%	1 2.3%	6 3.7%
Not Hispanic or Latino	31 93.9%	82 96.5%	43 97.7%	156 96.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 1.2%	0 0%	1 0.6%
Asian	0 0%	7 8.2%	6 13.6%	13 8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	2 6.1%	3 3.5%	2 4.5%	7 4.3%
White	31 93.9%	74 87.1%	36 81.8%	141 87%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Phase 1: To Determine the Recommended Phase 2 Dose of the MM-121 + Erlotinib Combination Based Upon Either the Maximum Tolerated Dose (MTD) or the Maximum Feasible Dose of the Combination in Patients With NSCLC.
Description	To establish the safety of escalating doses of MM-121 in combination with erlotinib in order to determine the recommended phase 2 dose of the combination for the second part of the study. Dose-escalation conducted using standard 3+3 model to determine maximum tolerated dose. Reports of Dose-Limiting Toxicities (DLTs) were assessed to determine the MTD.
Time Frame	From date of first dose to 30 days after termination, the longest 175 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7
Arm/Group Description	MM-121 6 mk/kg (Q2W IV) and 100 mg erlotinib (daily PO)	6 mg/kg MM-121 Q2W + 150 mg erlotinib (daily PO)	MM-121 12 mg/kg (Q2W IV) + 100 mg erlotinib (daily PO)	MM-121 12 mg/kg (Q2W IV) + 150 mg erlotinib (PO daily)	MM-121 20 mg/kg (weekly IV) + erlotinib 100 mg (PO daily)	MM-121 20 mg/kg (Q2W IV) + erlotinib 100 mg (PO daily)	MM-121 20 mg/kg (Q3W IV) + erlotinib 100 mg (PO daily)
Measure Participants	1	3	6	3	6	8	6
Number [participants reporting DLTs]	0 0%	0 0%	1 2.3%	1 0.6%	1 NaN	0 NaN	0 NaN

2. Primary Outcome

Title	Phase 1: Determine the Maximum Tolerated Dose Dependent on Reports of Dose-limiting Toxicities
Description	Using a 3+3 dose escalation model, the maximum tolerated dose was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in the expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was used as the recommended Phase 2 dose.
Time Frame	From date of first dose to 30 days after termination, the longest 175 weeks

Outcome Measure Data

Analysis Population Description

All participants treated in the Phase 1 dose-escalation portion of the study

Arm/Group Title	Phase 1: All Participants
Arm/Group Description	All participants in the dose escalation portion of the Phase 1
Measure Participants	33
Number [dose level of MTD]	NA

3. Primary Outcome

Title	Phase 2: Progression-free Survival of the MM-121 + Erlotinib Combination
Description	This was a time-to-event measure using Progression-Free Survival (PFS) comparing MM-121 + erlotinib vs.erlotinib alone. Progression of disease is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions". Progression free survival was defined as the number of weeks from the date of randomization to the date of death or progression. If neither death nor progression was observed during the study, PFS data was censored at the last non-progressive disease valid tumor assessment unless the patient was discontinued due to symptomatic deterioration. If this occurred, the patient was counted as having progressive disease (PD).
Time Frame	Time from first dose to date of progression, with a median of 8.1 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MM-121 + Erlotinib	Erlotinib
Arm/Group Description	EGFR wild-type, EGFR-TKI naive patients randomized to receive: MM-121 every other week at a dose of 20 mg/kg IV in combination with daily 100 mg erlotinib p.o.	EGFR wild-type, EGFR-TKI naive patients randomized to receive: daily 150 mg erlotinib p.o. alone
Measure Participants	85	44
Median (95% Confidence Interval) [weeks]	8.1	7.7

4. Post-Hoc Outcome

Title	To Explore the Utility of an EGFR Family Receptor-ligand (Heregulin, HRG) as a Predictor of Response to MM-121 and /or Erlotinib in Formalin Fixed (FFPE) Tumor Samples
Description	Tumor tissue samples were obtained from patients prior to enrollment. Samples were analyzed using RNA-ISH for the expression of the biomarker, heregulin. Progression-free survival was assessed using RECIST v 1.1 to determine whether patients whose tumors express HRG have a lower PFS than those whose tumors do not express HRG, and to assess whether the addition of MM-121 to erlotinib can increase PFS in HRG-high patients.
Time Frame	Time from first dose to date of progression, with a median of 8.1 weeks

Outcome Measure Data

Analysis Population Description

Patients with available tissue for heregulin testing

Arm/Group Title	HRG High: MM-121 + Erlotinib	HRG High: Erlotinib	HRG Low: Erlotinib	HRG Low: MM-121 + Erlotinib
Arm/Group Description	EGFR wild-type, EGFR-TKI naive patients randomized to receive: MM-121 every other week at a dose of 20 mg/kg IV in combination with daily 100 mg erlotinib p.o.	EGFR wild-type, EGFR-TKI naive patients randomized to receive: daily 150 mg erlotinib p.o. alone	EGFR wild-type, EGFR-TKI naive patients randomized to receive: daily 150 mg erlotinib p.o. alone	EGFR wild-type, EGFR-TKI naive patients randomized to receive: MM-121 every other week at a dose of 20 mg/kg IV in combination with daily 100 mg erlotinib p.o.
Measure Participants	23	13	12	20
Median (95% Confidence Interval) [months PFS]	1.9	1.7	2.3	1.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 1, Cohort 2
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.008
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.35
	Confidence Interval	(2-Sided) 95%; 0.16 to 0.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cohort 3, Cohort 4
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.059
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.15
	Confidence Interval	(2-Sided) 95%; 0.97 to 4.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	AEs were collected from a patient's first dose until 30 days after treatment termination. SAEs were collected from time of informed consent until 30 days after termination. If related, events could be reported at any time after termination.
Adverse Event Reporting Description	All related AEs ongoing at the time of treatment discontinuation were followed until resolution. Investigators were to report any AEs/SAEs assumed to be related any time, even if occurring more than 30 days after last dose. Though different for each patient, on average, patients could be followed for related AEs/SAEs for ~1 year after termination.
Arm/Group Title	Ph 2: MM-121 + Erlotinib		Ph 2: Erlotinib		Ph 1: MM-121 + Erlotinib
Arm/Group Description	EGFR wild-type, EGFR-TKI naive patients randomized to receive: MM-121 every other week at a dose of 20 mg/kg IV in combination with daily 100 mg erlotinib p.o.		EGFR wild-type, EGFR-TKI naive patients randomized to receive: daily 150 mg erlotinib p.o. alone		Escalating Doses of MM-121 + erlotinib
All Cause Mortality
	Ph 2: MM-121 + Erlotinib		Ph 2: Erlotinib		Ph 1: MM-121 + Erlotinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Ph 2: MM-121 + Erlotinib		Ph 2: Erlotinib		Ph 1: MM-121 + Erlotinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	40/85 (47.1%)		18/44 (40.9%)		16/33 (48.5%)
Blood and lymphatic system disorders
Anemia	0/85 (0%)		0/44 (0%)		1/33 (3%)
Cardiac disorders
Cardiac Arrest	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Cardiopulmonary Failure	0/85 (0%)		1/44 (2.3%)		0/33 (0%)
Intracardiac Thrombus	0/85 (0%)		1/44 (2.3%)		0/33 (0%)
Tachycardia	0/85 (0%)		1/44 (2.3%)		1/33 (3%)
Ventricular Fibrillation	0/85 (0%)		1/44 (2.3%)		0/33 (0%)
Cardiac Tamponade	0/85 (0%)		0/44 (0%)		2/33 (6.1%)
Gastrointestinal disorders
Diarrhea	2/85 (2.4%)		1/44 (2.3%)		1/33 (3%)
Gastritis	2/85 (2.4%)		0/44 (0%)		0/33 (0%)
Abdominal Pain	0/85 (0%)		1/44 (2.3%)		0/33 (0%)
Abdominal Pain Upper	0/85 (0%)		1/44 (2.3%)		0/33 (0%)
Ileus	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Small Intestinal Obstruction	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Vomiting	0/85 (0%)		1/44 (2.3%)		0/33 (0%)
Stomatitis	0/85 (0%)		0/44 (0%)		1/33 (3%)
General disorders
Disease Progression	14/85 (16.5%)		3/44 (6.8%)		1/33 (3%)
Chest Pain	1/85 (1.2%)		1/44 (2.3%)		0/33 (0%)
Asthenia	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Gait Disturbance	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Fatigue	0/85 (0%)		0/44 (0%)		1/33 (3%)
Pain	0/85 (0%)		0/44 (0%)		1/33 (3%)
Infections and infestations
Pneumonia	4/85 (4.7%)		4/44 (9.1%)		1/33 (3%)
Bronchopneumonia	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Klebsiella Infection	0/85 (0%)		1/44 (2.3%)		0/33 (0%)
Localized Infection	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Scrotal Infection	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Sepsis	1/85 (1.2%)		0/44 (0%)		1/33 (3%)
Septic Shock	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Upper Respiratory Tract Infection	0/85 (0%)		1/44 (2.3%)		0/33 (0%)
Urinary Tract Infection	0/85 (0%)		0/44 (0%)		2/33 (6.1%)
Bronchitis	0/85 (0%)		0/44 (0%)		1/33 (3%)
Injury, poisoning and procedural complications
Pelvic Fracture	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Investigations
General Physical Condition Abnormal	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
International Normalized Ratio Increased	1/85 (1.2%)		0/44 (0%)		1/33 (3%)
Electrocardiogram QT prolonged	0/85 (0%)		0/44 (0%)		1/33 (3%)
Metabolism and nutrition disorders
Dehydration	1/85 (1.2%)		1/44 (2.3%)		2/33 (6.1%)
Failure to thrive	0/85 (0%)		0/44 (0%)		1/33 (3%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Back Pain	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Bone Pain	0/85 (0%)		1/44 (2.3%)		0/33 (0%)
Musculoskeletal chest pain	0/85 (0%)		1/44 (2.3%)		0/33 (0%)
Groin Pain	0/85 (0%)		0/44 (0%)		1/33 (3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm Progression	1/85 (1.2%)		1/44 (2.3%)		0/33 (0%)
Colon Cancer	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Lung Neoplasm Malignant	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Metastases to Central Nervous System	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Pituitary Tumor Benign	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Non-small cell lung cancer	0/85 (0%)		0/44 (0%)		1/33 (3%)
Pericardial effusion	0/85 (0%)		0/44 (0%)		0/33 (0%)
Nervous system disorders
Cerebral Infarction	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Cerebrovascular accident	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Complex Partial Seizures	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Dizziness	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Spinal Cord Compression	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Psychiatric disorders
Mental Status Changes	0/85 (0%)		0/44 (0%)		1/33 (3%)
Renal and urinary disorders
Renal Failure Acute	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Reproductive system and breast disorders
Pelvic Pain	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	4/85 (4.7%)		3/44 (6.8%)		0/33 (0%)
Pulmonary Embolism	3/85 (3.5%)		1/44 (2.3%)		3/33 (9.1%)
Pleural Effusion	2/85 (2.4%)		1/44 (2.3%)		0/33 (0%)
Aspiration	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Chronic Obstructive Pulmonary Disease	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Hypoxia	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Pneumonitis	0/85 (0%)		1/44 (2.3%)		0/33 (0%)
Respiratory Failure	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Acute Respiratory Failure	0/85 (0%)		0/44 (0%)		1/33 (3%)
Acute Respiratory Distress Syndrome	0/85 (0%)		0/44 (0%)		1/33 (3%)
Skin and subcutaneous tissue disorders
Dermatitis Acneform	0/85 (0%)		1/44 (2.3%)		1/33 (3%)
Vascular disorders
Hemorrhage	1/85 (1.2%)		0/44 (0%)		0/33 (0%)
Deep Vein Thrombosis	0/85 (0%)		0/44 (0%)		1/33 (3%)
Orthostatic hypotension	0/85 (0%)		0/44 (0%)		1/33 (3%)
Venous Occlusion	0/85 (0%)		0/44 (0%)		1/33 (3%)
Other (Not Including Serious) Adverse Events
	Ph 2: MM-121 + Erlotinib		Ph 2: Erlotinib		Ph 1: MM-121 + Erlotinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	85/85 (100%)		44/44 (100%)		33/33 (100%)
Blood and lymphatic system disorders
Anemia	9/85 (10.6%)		4/44 (9.1%)		7/33 (21.2%)
Thrombocytopenia	2/85 (2.4%)		0/44 (0%)		2/33 (6.1%)
Cardiac disorders
TACHYCARDIA	1/85 (1.2%)		1/44 (2.3%)		3/33 (9.1%)
CARDIAC TAMPONADE	0/85 (0%)		0/44 (0%)		2/33 (6.1%)
PERICARDIAL EFFUSION	1/85 (1.2%)		0/44 (0%)		2/33 (6.1%)
SUPRAVENTRICULAR TACHYCARDIA	2/85 (2.4%)		0/44 (0%)		2/33 (6.1%)
Eye disorders
CONJUNCTIVITIS	3/85 (3.5%)		0/44 (0%)		4/33 (12.1%)
EYE PAIN	1/85 (1.2%)		0/44 (0%)		2/33 (6.1%)
EYE PRURITUS	0/85 (0%)		0/44 (0%)		2/33 (6.1%)
LACRIMATION INCREASED	1/85 (1.2%)		0/44 (0%)		2/33 (6.1%)
Gastrointestinal disorders
Diarrhea	59/85 (69.4%)		27/44 (61.4%)		27/33 (81.8%)
Nausea	29/85 (34.1%)		14/44 (31.8%)		9/33 (27.3%)
Vomiting	19/85 (22.4%)		11/44 (25%)		8/33 (24.2%)
Stomatitis	20/85 (23.5%)		5/44 (11.4%)		7/33 (21.2%)
Constipation	10/85 (11.8%)		7/44 (15.9%)		6/33 (18.2%)
Abdominal Pain	5/85 (5.9%)		1/44 (2.3%)		3/33 (9.1%)
Dysphagia	3/85 (3.5%)		0/44 (0%)		3/33 (9.1%)
Gastroesophageal reflux disease	2/85 (2.4%)		1/44 (2.3%)		4/33 (12.1%)
Abdominal Distension	1/85 (1.2%)		0/44 (0%)		2/33 (6.1%)
Abdominal Pain Upper	4/85 (4.7%)		2/44 (4.5%)		2/33 (6.1%)
CHEILITIS	0/85 (0%)		0/44 (0%)		2/33 (6.1%)
DRY MOUTH	3/85 (3.5%)		0/44 (0%)		2/33 (6.1%)
ORAL DISCOMFORT	0/85 (0%)		0/44 (0%)		2/33 (6.1%)
General disorders
Fatigue	31/85 (36.5%)		13/44 (29.5%)		21/33 (63.6%)
Disease Progression	14/85 (16.5%)		3/44 (6.8%)		1/33 (3%)
Asthenia	7/85 (8.2%)		6/44 (13.6%)		3/33 (9.1%)
Pyrexia	6/85 (7.1%)		7/44 (15.9%)		1/33 (3%)
Mucosal Inflammation	9/85 (10.6%)		3/44 (6.8%)		7/33 (21.2%)
Peripheral Edema	4/85 (4.7%)		3/44 (6.8%)		6/33 (18.2%)
Early Satiety	1/85 (1.2%)		0/44 (0%)		7/33 (21.2%)
Pain	0/85 (0%)		0/44 (0%)		4/33 (12.1%)
Chills	4/85 (4.7%)		1/44 (2.3%)		2/33 (6.1%)
Hepatobiliary disorders
hyperbilirubinemia	3/85 (3.5%)		1/44 (2.3%)		2/33 (6.1%)
Infections and infestations
Pneumonia	6/85 (7.1%)		6/44 (13.6%)		2/33 (6.1%)
Paronychia	9/85 (10.6%)		2/44 (4.5%)		7/33 (21.2%)
Urinary Tract Infection	4/85 (4.7%)		4/44 (9.1%)		9/33 (27.3%)
Nasopharyngitis	3/85 (3.5%)		3/44 (6.8%)		0/33 (0%)
CANDIDIASIS	0/85 (0%)		0/44 (0%)		3/33 (9.1%)
FUNGAL SKIN INFECTION	2/85 (2.4%)		1/44 (2.3%)		3/33 (9.1%)
UPPER RESPIRATORY TRACT	4/85 (4.7%)		1/44 (2.3%)		3/33 (9.1%)
VULVOVAGINAL MYCOTIC INFECTION	0/85 (0%)		0/44 (0%)		3/33 (9.1%)
NAIL INFECTION	1/85 (1.2%)		0/44 (0%)		2/33 (6.1%)
Oral Herpes	3/85 (3.5%)		0/44 (0%)		2/33 (6.1%)
Sepsis	1/85 (1.2%)		0/44 (0%)		2/33 (6.1%)
Injury, poisoning and procedural complications
Excoriation	0/85 (0%)		0/44 (0%)		2/33 (6.1%)
Skin laceration	0/85 (0%)		0/44 (0%)		2/33 (6.1%)
Investigations
Weight Decreased	27/85 (31.8%)		11/44 (25%)		9/33 (27.3%)
Blood Creatinine Increased	7/85 (8.2%)		3/44 (6.8%)		2/33 (6.1%)
Aspartate Aminotransferase Increased	6/85 (7.1%)		2/44 (4.5%)		2/33 (6.1%)
Alanine Aminotransferase Increased	6/85 (7.1%)		1/44 (2.3%)		1/33 (3%)
Blood Magnesium Decreased	6/85 (7.1%)		0/44 (0%)		0/33 (0%)
Blook Alkaline Phosphatase Increased	5/85 (5.9%)		0/44 (0%)		3/33 (9.1%)
Electrocardiogram QT prolonged	0/85 (0%)		0/44 (0%)		3/33 (9.1%)
ACTIVATED PARTIAL THROMBOPLASTIN TIME PROLONGED	1/85 (1.2%)		0/44 (0%)		2/33 (6.1%)
Breath Sounds Abnormal	1/85 (1.2%)		1/44 (2.3%)		2/33 (6.1%)
Metabolism and nutrition disorders
Decreased Appetite	37/85 (43.5%)		16/44 (36.4%)		11/33 (33.3%)
Hypokalemia	14/85 (16.5%)		3/44 (6.8%)		8/33 (24.2%)
Dehydration	7/85 (8.2%)		5/44 (11.4%)		11/33 (33.3%)
Hypomagnesemia	6/85 (7.1%)		3/44 (6.8%)		8/33 (24.2%)
Hyperglycemia	5/85 (5.9%)		1/44 (2.3%)		0/33 (0%)
Hyponatremia	3/85 (3.5%)		1/44 (2.3%)		3/33 (9.1%)
HYPOPHOSPHATAEMIA	0/85 (0%)		1/44 (2.3%)		3/33 (9.1%)
HYPERKALAEMIA	0/85 (0%)		2/44 (4.5%)		2/33 (6.1%)
HYPOCALCAEMIA	1/85 (1.2%)		1/44 (2.3%)		2/33 (6.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	9/85 (10.6%)		4/44 (9.1%)		6/33 (18.2%)
Musculoskeletal pain	8/85 (9.4%)		3/44 (6.8%)		3/33 (9.1%)
Musculoskeletal chest pain	6/85 (7.1%)		3/44 (6.8%)		1/33 (3%)
Pain in Extremity	3/85 (3.5%)		1/44 (2.3%)		6/33 (18.2%)
Back Pain	15/85 (17.6%)		4/44 (9.1%)		5/33 (15.2%)
Muscle Spasms	1/85 (1.2%)		1/44 (2.3%)		4/33 (12.1%)
Muscle weakness	2/85 (2.4%)		1/44 (2.3%)		4/33 (12.1%)
Flank Pain	1/85 (1.2%)		1/44 (2.3%)		2/33 (6.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
METASTASES TO CENTRAL NERVOUS SYSTEM	2/85 (2.4%)		0/44 (0%)		2/33 (6.1%)
Nervous system disorders
Dizziness	11/85 (12.9%)		8/44 (18.2%)		4/33 (12.1%)
Dysgeusia	14/85 (16.5%)		1/44 (2.3%)		6/33 (18.2%)
Headache	7/85 (8.2%)		3/44 (6.8%)		3/33 (9.1%)
NEUROPATHY PERIPHERAL	2/85 (2.4%)		1/44 (2.3%)		3/33 (9.1%)
AMNESIA	0/85 (0%)		0/44 (0%)		2/33 (6.1%)
PARAESTHESIA	3/85 (3.5%)		2/44 (4.5%)		2/33 (6.1%)
SYNCOPE	1/85 (1.2%)		0/44 (0%)		2/33 (6.1%)
Psychiatric disorders
Anxiety	8/85 (9.4%)		2/44 (4.5%)		4/33 (12.1%)
Depression	5/85 (5.9%)		3/44 (6.8%)		2/33 (6.1%)
Insomnia	5/85 (5.9%)		1/44 (2.3%)		12/33 (36.4%)
Confusional State	1/85 (1.2%)		3/44 (6.8%)		0/33 (0%)
Agitation	0/85 (0%)		0/44 (0%)		2/33 (6.1%)
Renal and urinary disorders
Dysuria	2/85 (2.4%)		0/44 (0%)		5/33 (15.2%)
HAEMATURIA	0/85 (0%)		0/44 (0%)		2/33 (6.1%)
NOCTURIA	1/85 (1.2%)		0/44 (0%)		2/33 (6.1%)
PROTEINURIA	1/85 (1.2%)		0/44 (0%)		2/33 (6.1%)
Reproductive system and breast disorders
Breast Pain	0/85 (0%)		0/44 (0%)		2/33 (6.1%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	22/85 (25.9%)		9/44 (20.5%)		6/33 (18.2%)
Cough	16/85 (18.8%)		6/44 (13.6%)		12/33 (36.4%)
Dysphonia	10/85 (11.8%)		1/44 (2.3%)		4/33 (12.1%)
Epistaxis	10/85 (11.8%)		1/44 (2.3%)		6/33 (18.2%)
Productive Cough	6/85 (7.1%)		2/44 (4.5%)		1/33 (3%)
Dyspnea Exertional	2/85 (2.4%)		0/44 (0%)		6/33 (18.2%)
Oropharyngeal Pain	4/85 (4.7%)		1/44 (2.3%)		4/33 (12.1%)
WHEEZING	2/85 (2.4%)		0/44 (0%)		4/33 (12.1%)
HAEMOPTYSIS	4/85 (4.7%)		0/44 (0%)		3/33 (9.1%)
PULMONARY EMBOLISM	3/85 (3.5%)		2/44 (4.5%)		3/33 (9.1%)
RHINORRHOEA	4/85 (4.7%)		1/44 (2.3%)		3/33 (9.1%)
RHONCHI	0/85 (0%)		1/44 (2.3%)		3/33 (9.1%)
SINUS DISORDER	0/85 (0%)		0/44 (0%)		3/33 (9.1%)
HYPOXIA	3/85 (3.5%)		0/44 (0%)		2/33 (6.1%)
Nasal Inflammation	0/85 (0%)		0/44 (0%)		2/33 (6.1%)
Skin and subcutaneous tissue disorders
Rash	46/85 (54.1%)		21/44 (47.7%)		15/33 (45.5%)
Dry Skin	28/85 (32.9%)		11/44 (25%)		11/33 (33.3%)
Dermatitis Acneform	14/85 (16.5%)		12/44 (27.3%)		12/33 (36.4%)
Pruritis	10/85 (11.8%)		10/44 (22.7%)		0/33 (0%)
Rash Maculo-papular	4/85 (4.7%)		4/44 (9.1%)		3/33 (9.1%)
Palmar-Plantar Erythrodysasthesia Syndrome	4/85 (4.7%)		3/44 (6.8%)		3/33 (9.1%)
Skin Disorder	5/85 (5.9%)		2/44 (4.5%)		1/33 (3%)
Skin Exfoliation	3/85 (3.5%)		3/44 (6.8%)		1/33 (3%)
Alopecia	5/85 (5.9%)		0/44 (0%)		3/33 (9.1%)
Skin Fissures	0/85 (0%)		3/44 (6.8%)		1/33 (3%)
ONYCHOCLASIS	3/85 (3.5%)		0/44 (0%)		4/33 (12.1%)
Skin Ulcer	0/85 (0%)		0/44 (0%)		2/33 (6.1%)
Vascular disorders
HYPERTENSION	1/85 (1.2%)		1/44 (2.3%)		2/33 (6.1%)
ORTHOSTATIC HYPOTENSION	0/85 (0%)		1/44 (2.3%)		2/33 (6.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.