Neoadjuvant MPDL3280A, Nab-paclitaxel and Carboplatin (MAC) in NSCLC

• ClinicalTrials.gov Identifier: NCT02716038
• Recruitment Status: Completed
• First Posted: March 22, 2016
• Results First Posted: December 12, 2023
• Last Update Posted: December 12, 2023
• Sponsor: Columbia University
• Collaborators: Genentech, Inc.; Celgene Corporation
• Information provided by (Responsible Party): Columbia University

• 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
• Interventions: Drug: MPDL3280A; Drug: Carboplatin; Drug: Nab-paclitaxel
• Enrollment: 39

Participant Flow

Recruitment Details
Pre-assignment Details	8 patients did not continue after enrollment onto protocol regimen (7 screen fails and 1 subject withdrawal)

Arm/Group Title	MPDL3280A, Carboplatin, Nab-paclitaxel
Arm/Group Description	Subjects with advanced or recurrent cancers receiving: MPDL3280A every 21 days for up to 84 days; Carboplatin every 21 days for up to 84 days; Nab-paclitaxel every 7 days for up to 84 days
Period Title: Overall Study
Started	31
Completed	26
Not Completed	5
Reason Not Completed
Not evaluable	1
Not brought to surgery due to brain metastasis	1
Unresectable	3

Baseline Characteristics

Arm/Group Title		MPDL3280A, Carboplatin, Nab-paclitaxel
Arm/Group Description		Subjects with advanced or recurrent cancers receiving: MPDL3280A every 21 days for up to 84 days; Carboplatin every 21 days for up to 84 days; Nab-paclitaxel every 7 days for up to 84 days
Overall Number of Baseline Participants		31
Baseline Analysis Population Description		[Not Specified]
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	31 participants
40-49 years		2 6.5%
50-59 years		3 9.7%
60-69 years		12 38.7%
70-79 years		13 41.9%
80-89 years		1 3.2%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	31 participants
	Female	15 48.4%
	Male	16 51.6%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	31 participants
	Hispanic or Latino	3 9.7%
	Not Hispanic or Latino	17 54.8%
	Unknown or Not Reported	11 35.5%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	31 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	2 6.5%
	White	19 61.3%
	More than one race	0 0.0%
	Unknown or Not Reported	10 32.3%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	31 participants
		31

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Major Pathologic Response (MPR)
Description	Major pathologic response rate (MPR) is defined as > or = 90% decrease in viable tumor.
Time Frame	84 days

Outcome Measure Data

Analysis Population Description

26 out of 31 enrolled participants had surgery (resectable) and evaluable data.

Arm/Group Title	MPDL3280A, Carboplatin, Nab-paclitaxel
Arm/Group Description:	Subjects with advanced or recurrent cancers receiving: MPDL3280A every 21 days for up to 84 days; Carboplatin every 21 days for up to 84 days; Nab-paclitaxel every 7 days for up to 84 days
Overall Number of Participants Analyzed	26
Measure Type: Count of Participants; Unit of Measure: Participants
	17 65.4%

Adverse Events

Time Frame	Up to 48 months for the 31 out of the 39 enrolled/consented had continued onto protocol regimen, and 30 out of 31 had evaluable data (i.e., 1 patient determined not evaluable).
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	MPDL3280A, Carboplatin, Nab-paclitaxel
Arm/Group Description	Subjects with advanced or recurrent cancers receiving: MPDL3280A every 21 days for up to 84 days; Carboplatin every 21 days for up to 84 days; Nab-paclitaxel every 7 days for up to 84 days
All-Cause Mortality
	MPDL3280A, Carboplatin, Nab-paclitaxel
	Affected / at Risk (%)
Total	0/30 (0.00%)
Serious Adverse Events
	MPDL3280A, Carboplatin, Nab-paclitaxel
	Affected / at Risk (%)
Total	3/30 (10.00%)
Blood and lymphatic system disorders
Febrile neutropenia * [1]	1/30 (3.33%)
Metabolism and nutrition disorders
Hyperglycemia * [2]	1/30 (3.33%)
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage * [3]	1/30 (3.33%)
* Indicates events were collected by non-systematic assessment; [1] Grade 3; [2] Grade 4; [3] Grade 2
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	MPDL3280A, Carboplatin, Nab-paclitaxel
	Affected / at Risk (%)
Total	21/30 (70.00%)
Blood and lymphatic system disorders
Neutropenia *	15/30 (50.00%)
Thrombocytopenia *	2/30 (6.67%)
Investigations
Alanine aminotransferase increased *	2/30 (6.67%)
Aspartate aminotransferase increased *	2/30 (6.67%)
* Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Catherine A. Shu, MD
• Organization: Columbia University Irving Medical Center
• Phone: 212-305-3997
• EMail: cas2145@cumc.columbia.edu

Publications:

Pataer A, Kalhor N, Correa AM, Raso MG, Erasmus JJ, Kim ES, Behrens C, Lee JJ, Roth JA, Stewart DJ, Vaporciyan AA, Wistuba II, Swisher SG; University of Texas M. D. Anderson Lung Cancer Collaborative Research Group. Histopathologic response criteria predict survival of patients with resected lung cancer after neoadjuvant chemotherapy. J Thorac Oncol. 2012 May;7(5):825-32. doi: 10.1097/JTO.0b013e318247504a.

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90. doi: 10.3322/caac.20107. Epub 2011 Feb 4. Erratum In: CA Cancer J Clin. 2011 Mar-Apr;61(2):134.

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015 Jan-Feb;65(1):5-29. doi: 10.3322/caac.21254. Epub 2015 Jan 5.

Langer CJ, Besse B, Gualberto A, Brambilla E, Soria JC. The evolving role of histology in the management of advanced non-small-cell lung cancer. J Clin Oncol. 2010 Dec 20;28(36):5311-20. doi: 10.1200/JCO.2010.28.8126. Epub 2010 Nov 15.

Goldstraw P, Crowley J, Chansky K, Giroux DJ, Groome PA, Rami-Porta R, Postmus PE, Rusch V, Sobin L; International Association for the Study of Lung Cancer International Staging Committee; Participating Institutions. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol. 2007 Aug;2(8):706-14. doi: 10.1097/JTO.0b013e31812f3c1a. Erratum In: J Thorac Oncol. 2007 Oct;2(10):985.

Pignon JP, Tribodet H, Scagliotti GV, Douillard JY, Shepherd FA, Stephens RJ, Dunant A, Torri V, Rosell R, Seymour L, Spiro SG, Rolland E, Fossati R, Aubert D, Ding K, Waller D, Le Chevalier T; LACE Collaborative Group. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol. 2008 Jul 20;26(21):3552-9. doi: 10.1200/JCO.2007.13.9030. Epub 2008 May 27.

NSCLC Meta-analyses Collaborative Group; Arriagada R, Auperin A, Burdett S, Higgins JP, Johnson DH, Le Chevalier T, Le Pechoux C, Parmar MK, Pignon JP, Souhami RL, Stephens RJ, Stewart LA, Tierney JF, Tribodet H, van Meerbeeck J. Adjuvant chemotherapy, with or without postoperative radiotherapy, in operable non-small-cell lung cancer: two meta-analyses of individual patient data. Lancet. 2010 Apr 10;375(9722):1267-77. doi: 10.1016/S0140-6736(10)60059-1. Epub 2010 Mar 24.

NSCLC Meta-analysis Collaborative Group. Preoperative chemotherapy for non-small-cell lung cancer: a systematic review and meta-analysis of individual participant data. Lancet. 2014 May 3;383(9928):1561-71. doi: 10.1016/S0140-6736(13)62159-5. Epub 2014 Feb 25.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Shi Y, Li J, Chen M, Liu H, Ma D, Lin Y, Wang M, Xu Y. Sarcoidosis-like reaction after neoadjuvant pembrolizumab combined with chemotherapy mimicking disease progression of NSCLC induced encouraging discovery of pathological complete response. Thorac Cancer. 2021 Dec;12(24):3433-3436. doi: 10.1111/1759-7714.14228. Epub 2021 Nov 11.

Shu CA, Gainor JF, Awad MM, Chiuzan C, Grigg CM, Pabani A, Garofano RF, Stoopler MB, Cheng SK, White A, Lanuti M, D'Ovidio F, Bacchetta M, Sonett JR, Saqi A, Rizvi NA. Neoadjuvant atezolizumab and chemotherapy in patients with resectable non-small-cell lung cancer: an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 2020 Jun;21(6):786-795. doi: 10.1016/S1470-2045(20)30140-6. Epub 2020 May 7.

• Responsible Party: Columbia University
• ClinicalTrials.gov Identifier: NCT02716038
• Other Study ID Numbers: AAAQ3153
• First Submitted: March 17, 2016
• First Posted: March 22, 2016
• Results First Submitted: October 1, 2023
• Results First Posted: December 12, 2023
• Last Update Posted: December 12, 2023