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

NCT02716038 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: AAAQ3153
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 3

Brief Summary

This is a research study to test the effectiveness of nab-paclitaxel + carboplatin + MPDL3280A for treatment of non-small-cell lung carcinoma (NSCLC), which is a type of lung cancer. The study aims to determine if chemotherapy combined with immune-based therapy can lead to improvement in tumor response rates over historical response rates with chemotherapy alone.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Non-Small Cell Lung Cancer; Non-Small-Cell Lung Carcinoma; Nonsmall Cell Lung Cancer; NSCLC

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With Major Pathologic Response (MPR)

  Major pathologic response rate (MPR) is defined as \> or = 90% decrease in viable tumor.

  84 days

Study Arms (1)

MPDL3280A, Carboplatin, Nab-paclitaxel

EXPERIMENTAL

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

Drug: MPDL3280A; Drug: Carboplatin; Drug: Nab-paclitaxel

Interventions

MPDL3280A DRUG

MPDL3280A is a human, Fc optimized, monoclonal antibody directed against the protein ligand programmed cell death-1 ligand 1 (PD-L1), with potential immune checkpoint inhibitory and antineoplastic activities. Atezolizumab binds to PD-L1, blocking its binding to and activation of its receptor programmed death 1 (PD-1) expressed on activated T-cells, which may enhance the T-cell-mediated immune response to neoplasms and reverse T-cell inactivation. MPDL3280A 1200 mg will be administered as a 60 minute IV infusion on first administration, then over 30 minutes subsequently if tolerated.

Also known as: Atezolizumab, RG7446

MPDL3280A, Carboplatin, Nab-paclitaxel

Carboplatin DRUG

Carboplatin is a second-generation platinum compound with a broad spectrum of antineoplastic properties. Carboplatin contains a platinum atom complexed with two ammonia groups and a cyclobutane-dicarboxyl residue. This agent is activated intracellularly to form reactive platinum complexes that bind to nucleophilic groups, thereby inducing intrastrand and interstrand DNA cross-links, as well as DNA-protein cross-links. These carboplatin-induced DNA and protein effects result in apoptosis and cell growth inhibition. Carboplatin area under the curve (AUC)=6 will be administered as a 30 minute IV infusion immediately after nab-paclitaxel.

Also known as: Paraplatin, Paraplatin-Aqueous (AQ)

MPDL3280A, Carboplatin, Nab-paclitaxel

Nab-paclitaxel DRUG

Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of the natural taxane paclitaxel with antineoplastic activity. Nab-paclitaxel binds to and stabilizes microtubules, preventing their depolymerization and so inhibiting cellular motility, mitosis, and replication. Nab-paclitaxel 100 mg/m2 will be administered as a 30 minute IV infusion.

Also known as: Abraxane

MPDL3280A, Carboplatin, Nab-paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have pathologically confirmed non-small cell lung cancer, of either squamous or non-squamous histology.
• Stage 1B-3A
• Deemed surgically resectable by a thoracic surgeon
• Age ≥ 18 years
• Radiologically measurable disease, as defined by response evaluation criteria in solid tumours (RECIST) v1.1
• Ability to understand and the willingness to sign a written informed consent document
• Females of child-bearing potential must:
• Either commit to true abstinence from heterosexual contact, or agree to use, and be able to comply with, effective contraception (\</=1% failure rate annually) without interruption, 28 days prior to starting therapy (including dose interruptions), and while on study medication or for a period of 90 days following treatment completion.
• Have a negative serum pregnancy test (β -hCG) result at screening and agree to ongoing pregnancy testing during the course of the study, and after the end of study therapy.
• Male subjects must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 6 months following treatment discontinuation, even if he has undergone a successful vasectomy.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (blocks are preferred) or at least 10 unstained slides, with an associated pathology report, for central testing of tumor PD-L1 expression
• Tumor tissue should be of good quality based on total and viable tumor content.
• Patients who do not have tissue specimens meeting eligibility requirements may undergo a biopsy during the screening period.
• Adequate organ and marrow function as defined below:

You may not qualify if:

• Any approved anticancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, within 5 years prior to initiation of study treatment; however, the following are allowed:
• Hormone-replacement therapy or oral contraceptives
• Herbal therapy \> 1 week prior to Cycle 1, Day 1 (herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to Cycle 1, Day 1)
• Malignancies other than the disease under study within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome or undergoing active surveillance per standard-of-care management (e.g., chronic lymphocytic leukemia Rai Stage 0, prostate cancer with Gleason score ≤ 6, and prostate-specific antigen (PSA) ≤ 10 mg/mL, etc.)
• Patients who are receiving any other investigational agents concurrently.
• Patients with no smoking history
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to MPDL3280A, carboplatin, or paclitaxel.
• Patients with active hepatitis B or C infections or a history of HIV infection.
• Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen (HBsAg) test and a positive for the antibody test to detect antibodies to hepatitis B core antigen (anti-HBc) are eligible.
• Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection including tuberculosis (TB), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
• Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• History or risk of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis
• Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible.

Sponsors & Collaborators

• Columbia University: lead
• Genentech, Inc.: collaborator
• Celgene Corporation: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Related Publications (10)

• 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.

  PMID: 22481232 BACKGROUND

• 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.

  PMID: 21296855 BACKGROUND

• 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.

  PMID: 25559415 BACKGROUND

• 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.

  PMID: 21079145 BACKGROUND

• 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.

  PMID: 17762336 BACKGROUND

• 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.

  PMID: 18506026 BACKGROUND

• 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.

  PMID: 20338627 BACKGROUND

• 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.

  PMID: 24576776 BACKGROUND

• 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.

  PMID: 34761878 DERIVED

• 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.

  PMID: 32386568 DERIVED

Related Links

• Howlader N, Noone AM, Krapcho M. SEER Cancer Statistics Review, 1975-2011. Based on November 2013 SEER data submission, posted to the SEER web site, April 2014.

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

atezolizumab; Carboplatin; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Catherine A. Shu, MD
• Organization: Columbia University Irving Medical Center

cas2145@cumc.columbia.edu

212-305-3997

Study Officials

• Catherine Shu, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2016
• First Posted: March 22, 2016
• Study Start: June 7, 2016
• Primary Completion: October 1, 2022
• Study Completion: October 1, 2022
• Last Updated: December 12, 2023
• Results First Posted: December 12, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)