MK-3475 in Combination With Docetaxel vs Docetaxel Alone in Non-Small Cell Lung Cancer Patients

NCT02574598 | Completed Phase 2 Results

• 1 other identifier: INCAN/014/033/ICI
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II open-label randomized clinical trial of MK-3475 (Pembrolizumab) on previously treated non-small cell lung cancer (NSCLC) patients . This drug has shown to allow partial response according to the immune-related response criteria and the response evaluation criteria in solid tumors (RECIST). The main endpoint is to compare the overall response rate (ORR) of MK-3475 with docetaxel or docetaxel alone in patients with advanced NSCLC.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

PDL1; monoclonal antibody

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  The objective response rate (ORR) per response evaluation criteria in solit tumors (RECIST v1.1) was defined as the sum of complete response or partial response assessed by RECIST (v1.1) and is presented as the percent of participants with 95% Confidence Intervals (CI). Complete response (CR) was considered if there was a dissapearance of all target lesions, any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to \<10 mm. Partial response (PR) was considered if there was at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR = CR + PR.

  from baseline to 2 months of treatment

Study Arms (2)

Docetaxel + MK-3475

EXPERIMENTAL

Docetaxel 75 mg/m2 every 3 weeks until progression of disease MK-3475 (administered on day 8) 200mg every 3 until progression of disease

Drug: MK-3475; Drug: Docetaxel

Docetaxel

ACTIVE COMPARATOR

Docetaxel 75 mg/m2 every 3 weeks until progression of disease followed by MK-3475 200mg every 3 until progression of disease

Drug: MK-3475; Drug: Docetaxel

Interventions

MK-3475 DRUG

The dosing interval of pembrolizumab can be increased in case of toxicity.

Also known as: pembrolizumab

Docetaxel; Docetaxel + MK-3475

Docetaxel DRUG

Use on both arms as standard of care.

Also known as: taxotere

Docetaxel; Docetaxel + MK-3475

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent
• Patients should be signed and dated form of written informed consent approved by the IRB / IEC in accordance with regulatory and institutional guidelines. This must be obtained before performing any procedure related to the protocol that are not part of the normal care of the patient.
• Patients must be willing and able to comply with scheduled visits , treatment program , laboratory testing including filling of questionnaires the results reported by the patient and other study requirements .
• Target Population
• Subjects with locally advanced NSCLC of squamous cell and non-squamous cell (adenocarcinoma and big cells) histological or cytologically documented , those who submit Stage IIIB / IV or recurrent disease after receiving radiation treatment or surgical resection
• Men and women ≥ 18 years of age.
• Performance status Eastern Cooperative Oncology Group ( ECOG ) ≤ 1.
• Subjects must have measurable disease by CT or MRI according to RECIST 1.1 criteria Radiographic Evaluation of Tumor on in the span of 28 days before randomization.
• The target lesions may be located on a previously irradiated field exists if documented progression of disease (radiographic) in that site. Subjects progression or recurrence of the disease must have experienced during or after prior chemotherapy regimen containing platinum in metastatic disease.
• This includes individuals who meet the following criteria:
• Subjects who received pemetrexed, bevacizumab or erlotinib as maintenance therapy (non-progressors double platinum-based chemotherapy) and progressed are eligible However, patients who received a wild EGFR tyrosine kinase inhibitor after failure of prior platinum-based therapy were excluded.
• Eligible patients who received double- platinum -based chemotherapy in adjuvant or neo adjuvant (after surgery and / or radiation) and developed recurrent or metastatic disease within 6 months after treatment ends
• Eligible individuals with recurrent disease \> 6 months after adjuvant chemotherapy or neoadjuvant platinum-based , who also subsequently progressed during or after one platinum-based doublet regimen to treat recurrences
• Subjects with a known mutation of EGFR and received EGFR TKI (erlotinib , gefitinib or experimental) and double platinum-based chemotherapy ( regardless of the order of administration).
• subjects with known ALK translocation double receiving platinum-based chemotherapy and ALK inhibitor ( crizotinib or experimental )

You may not qualify if:

• The subject must be excluded from participating in the trial if the subject:
• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.
• Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
• Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.

Sponsors & Collaborators

• Instituto Nacional de Cancerologia de Mexico: lead

Study Sites (1)

National Cancer Institute of Mexico

Mexico City, Mexico City, 14080, Mexico

Location

Related Publications (12)

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• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

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• Arrieta O, Barron F, Ramirez-Tirado LA, Zatarain-Barron ZL, Cardona AF, Diaz-Garcia D, Yamamoto Ramos M, Mota-Vega B, Carmona A, Peralta Alvarez MP, Bautista Y, Aldaco F, Gerson R, Rolfo C, Rosell R. Efficacy and Safety of Pembrolizumab Plus Docetaxel vs Docetaxel Alone in Patients With Previously Treated Advanced Non-Small Cell Lung Cancer: The PROLUNG Phase 2 Randomized Clinical Trial. JAMA Oncol. 2020 Jun 1;6(6):856-864. doi: 10.1001/jamaoncol.2020.0409.

  PMID: 32271354 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; Docetaxel

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)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Limitations and Caveats

The data here presented should be interpreted in light of its limitations. Foremost, the study was designed in the absence of recently established information, and therefore, several factors were not available during the patient selection process, including PD-L1 expression for all included patients. Additionally, patients with common oncogenic driver mutations, including EGFR could be enrolled. This generates a heterogeneous population with several already characterized subgroups present.

Results Point of Contact

• Title: Dr. Oscar Arrieta
• Organization: Instituto Nacional de Cancerología

ogar@unam.mx

(52) 55-5628-0400

Study Officials

• Oscar G Arrieta, MD, MSc

  National Institute of Cancer of Mexico

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Investigador en Ciencias Médicas "E"

Model Details: Patients will be randomly assigned (1:1) using a random numbers table to receive either monotherapy Docetaxel for 6 cycles or Pembrolizuymab plus Docetaxel for 6 cycles, following with maintenance therapy with Pembrolizumab until disease progression or unacceptable toxicity.

Study Record Dates

• First Submitted: October 9, 2015
• First Posted: October 14, 2015
• Study Start: June 1, 2016
• Primary Completion: October 1, 2019
• Study Completion: November 19, 2020
• Last Updated: January 6, 2021
• Results First Posted: December 14, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Once the information recruitment is concluded ( starting 6 months after publication)
• Access Criteria: Only information will be given to the principal investigator, with a signed request and registration of the protocol. For research and statistical purposes that are required. For future statistics publications related to this study.

Locations

ME (1)