Pembrolizumab With Nab-Paclitaxel in Non-Small Cell Lung Cancer

NCT02733250 | Completed Phase 1

• 1 other identifier: CE15.274
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine the optimal dose of nab-paclitaxel to be safely administered in combination with pembrolizumab in patients with advanced inoperable non-small cell lung cancer. The study is also aimed at evaluating the efficacy of the combination therapy.

Conditions

Lung Cancer

Keywords

NSCLC; Pembrolizumab; Nab-paclitaxel

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability of nab-paclitaxel in combination with pembrolizumab as measured by incidence of drug related adverse events (AEs), serious drug related AEs, dose-limiting toxicities.

  Safety analysis will be based on subjects who experienced toxicities as defined by the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. Safety will be assessed by quantifying the toxicities and grades experienced by subjects who received at least one dose of pembrolizumab and nab-paclitaxel, including serious adverse events (SAEs) and event of clinical interest (ECIs).

  Safety follow-up will be maintained up to 90 days following the administration of the last study-drug dose.

• Objective Response Rate (ORR)

  Defined as the proportion of patients with best overall response or either complete response or partial response, which will be recorded based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or the Immune related response criteria (irRC).

  up to 56 months

Study Arms (1)

Pembrolizumab + Nab-Paclitaxel

OTHER

Phase I will determine the recommended Phase II dose (RP2D) of nab-paclitaxel when given in combination with pembrolizumab. Escalation for nab-paclitaxel will be conducted following a "3+3" design. First cohort of 3 patients will receive nab-paclitaxel on Days 1 and 8 at a dose of 100 mg/m2 intravenous (IV) in combination with pembrolizumab at 200 mg IV every 3 weeks. If no dose limiting toxicities (DLT) occur, the dose of nab-paclitaxel will be escalated to 100 mg/m2 on Days 1, 8 and 15 every 3 weeks. The dose of pembrolizumab will remain the same. If no DLTs occur, dose level 2 will be defined as the RP2D. In the Phase II, pembrolizumab will be administered at 200 mg IV every 3 weeks and nab-paclitaxel will be administered at the RP2D.

Biological: Pembrolizumab; Drug: Nab-Paclitaxel

Interventions

Pembrolizumab BIOLOGICAL

200mg IV Day 1 of each 21 cycles

Also known as: Keytruda

Pembrolizumab + Nab-Paclitaxel

Nab-Paclitaxel DRUG

100mg/m2 IV Day 1, 8 and 15 of every 21 day cycles

Also known as: Abraxane

Pembrolizumab + Nab-Paclitaxel

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent for the trial.
• Be ≥ 18 years of age on day of signing informed consent.
• Have unresectable stage III (not eligible to curative-intent chemo-radiotherapy) or stage IV non-small cell lung cancer (NSCLC) according to the Clarification of Malignant Tumours (TNM) staging system for lung cancer (7th edition).
• Patients must be willing to undergo a biopsy procedure before the start of treatment unless these two conditions are met: 1) the biopsy must have been conducted after progression or intolerance to systemic first-line treatment as stated in criteria 7 and; 2) all the planned correlative analyses can be conducted on the available tissue.
• Have measurable/evaluable disease based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• Have an Eastern Cooperative Oncology Group (ECOG) of 0 or 1.

You may not qualify if:

• Has a known epidermal growth factor receptor (EGFR) sensitizing (activating) mutation and/or anaplastic lymphoma kinase (ALK) translocation.
• Has an unknown EGFR and ALK status.
• Has received prior therapy with paclitaxel or docetaxel for NSCLC.
• Has received systemic steroid therapy within three days prior to the first dose of study treatment or receiving any other form of systemic immunosuppressive medication.
• Has a history of allogeneic tissue/solid organ transplant.
• Has prior systemic cytotoxic chemotherapy, antineoplastic biological therapy, major surgery within 3 weeks of the first dose of study drug; received prior tyrosine kinase inhibitor therapy or completed palliative radiotherapy within 7 days of the first dose of study drug.
• Has an active infection requiring systemic therapy.
• Has received prior therapy with an anti-programmed cell death protein 1 (PD-1), including pembrolizumab, anti-programmed cell death protein ligand 1 (anti-PD-L1), anti-programmed cell death protein ligand 2 (anti-PD-L2), anti-tumor necrosis factor (CD137), or anticytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug targeting immune checkpoint pathways).
• Has had any other malignancy within 5 years prior to the start of therapy. Exceptions are malignancies with a negligible risk of metastasis or death (e.g., expected 5-year overall survival (OS) \> 90%).
• Has known active central nervous system (CNS) metastases or leptomeningeal involvement.
• Has active autoimmune disease (or documented history), or a syndrome that requires systemic corticosteroids or immunosuppressive agents (patients with auto-immune thyroid disease, vitiligo or well controlled type 1 diabetes mellitus are eligible).
• Has known history or active human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
• Women of childbearing potential who is unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 26 weeks after cessation of study drug.

Sponsors & Collaborators

• Centre hospitalier de l'Université de Montréal (CHUM): lead
• Centre de Recherche du Centre Hospitalier de l'Université de Montréal: collaborator
• Merck Canada Inc.: collaborator
• Celgene: collaborator
• Jewish General Hospital: collaborator

Study Sites (2)

Centre hospitalier de l'université de Montréal (CHUM)

Montreal, Quebec, H2X 3E4, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Related Publications (1)

• Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, Hon JK, Hirsh V, Bhar P, Zhang H, Iglesias JL, Renschler MF. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol. 2012 Jun 10;30(17):2055-62. doi: 10.1200/JCO.2011.39.5848. Epub 2012 Apr 30.

  PMID: 22547591 BACKGROUND

MeSH Terms

Conditions

Lung Neoplasms

Interventions

pembrolizumab; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Normand Blais, MD

  Centre hospitalier de l'Université de Montréal (CHUM)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2016
• First Posted: April 11, 2016
• Study Start: March 13, 2017
• Primary Completion: April 13, 2019
• Study Completion: December 13, 2019
• Last Updated: February 16, 2021

Record last verified: 2018-06

Locations

CA (2)