Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pembrolizumab + Idelalisib for Lung Cancer Study (PIL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03257722
Recruitment Status : Recruiting
First Posted : August 22, 2017
Last Update Posted : September 29, 2017
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Gilead Sciences
Information provided by (Responsible Party):
Zhonglin Hao, Augusta University

Brief Summary:
This is a phase 1b/2 study to determine the safety and effectiveness of the combination of pembrolizumab and idelalisib in NSCLC patients whose disease has stopped responding to immune therapy. This study is being done to see if adding another immune modulator (idelalisib) to standard pembrolizumab will increase response rates, compared to the response seen with pembrolizumab alone.

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Metastasis Recurrence Drug: Pembrolizumab Drug: Idelalisib Phase 1 Phase 2

Detailed Description:

This is a phase 1b/2 study to determine the safety and effectiveness of the combination of pembrolizumab and idelalisib in NSCLC patients whose disease has stopped responding to immune therapy. Pembrolizumab is an anti-PD-1 immunotherapy that is given intravenously and is approved for treatment of malignant NSCLC. Idelalisib is the first-in-class oral PI3K-δ inhibitor that is approved for treatment of certain forms of leukemia and lymphoma.

Immune checkpoint inhibitors (such as anti-PD-1) are effective in treating NSCLC as a single agent, but overall response isn't optimal; overall response rates (ORR) are only ~20% on average. The goal of this study is to see whether combining standard therapy with additional immune modulators will increase response rates, compared to the response seen with pembrolizumab monotherapy.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

This is an open labeled, single arm, interventional study combining standard pembrolizumab (MK-3475, trade name: Keytruda) with investigational agent, idelalisib (trade name: Zydelig) in non-small cell lung cancer (NSCLC). The study will enroll patients in two phases: a dose finding/tolerability assessment phase and an efficacy assessment phase.

The Phase 1b (modified 3+3 dose escalation) assessment will determine the safe dose of idelalisib in combination with pembrolizumab that down-regulates the activity of T-regulatory function (Treg).

The Phase 2 efficacy assessment will enroll patients to detect whether idelalisib added to pembrolizumab at the phase 2 recommended dose (P2RD) will result in further objective response.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib /II Trial of Pembrolizumab and Idelalisib in Patients With Non-small Cell Lung Cancer (NSCLC) Who Have Failed Immune Checkpoint Inhibitor
Actual Study Start Date : September 26, 2017
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : August 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Phase 1 Dose Escalation
Sequential cohorts of 3 patients will receive pembrolizumab 200 mg intravenously every 3 weeks, in addition to the oral drug, idelalisib, every day for 21 days. The first group of 3 will receive idelalisib 50 mg twice daily; the next cohort will receive idelalisib 100 mg twice daily; the last cohort will receive idelalisib 150 mg twice daily.
Drug: Pembrolizumab
Anti PD-1 immunotherapeutic agent, which blocks a protective mechanism on cancer cells to allow the immune system to destroy cancer cells. Administered intravenously (IV).
Other Names:
  • Keytruda
  • MK-3475

Drug: Idelalisib
Phosphatidylinositol 3-kinase (PI3K) inhibitor which promotes anti-tumor immune response. Administered orally (PO).
Other Names:
  • Zydelig
  • GS-1101

Experimental: Phase 2 Efficacy
All patients in the efficacy assessment phase will be treated with pembrolizumab (200 mg intravenously every 3 weeks) in combination with oral idelalisib (dose not exceeding 150 mg twice daily, per the phase 1 assessment) for 18 weeks before maintenance with pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years, until disease progression or unacceptable toxicity.
Drug: Pembrolizumab
Anti PD-1 immunotherapeutic agent, which blocks a protective mechanism on cancer cells to allow the immune system to destroy cancer cells. Administered intravenously (IV).
Other Names:
  • Keytruda
  • MK-3475

Drug: Idelalisib
Phosphatidylinositol 3-kinase (PI3K) inhibitor which promotes anti-tumor immune response. Administered orally (PO).
Other Names:
  • Zydelig
  • GS-1101




Primary Outcome Measures :
  1. Number of Participants With Dose-Limiting Toxicity (DLT) Events as Assessed by CTCAE v4.03 [ Time Frame: First 9 weeks at each dose level ]
    Modified 3+3 dose escalation design will be used to determine whether the addition of idelalisib to standard pembrolizumab is safe and tolerable in checkpoint inhibitor refractory NSCLC patients. An initial cohort of 3 patients will receive 50 mg twice daily idelalisib with standard pembrolizumab. If none of the 3 patients develop a DLT, another 3 patients will be enrolled. Dose will be escalated or de-escalated based on the occurrence of DLTs. All events will be assessed for possible, probable, or definite relation to idelalisib.


Secondary Outcome Measures :
  1. Dose-Finding Assessment for optimum dose of idelalisib in combination with pembrolizumab [ Time Frame: 18-27 weeks ]
    Determine the phase 2 recommended dose (P2RD) of idelalisib, in combination with pembrolizumab, in patients with checkpoint inhibitor refractory NSCLC. If no more than 1/6 patients in initial cohort develop a DLT, the patients will be tested for T-regulatory cell function suppression (80% suppression in 80% of patients). If dose is escalated or de-escalated, testing will continue to assess for optimal T-reg suppression. The dose at which the tolerability and suppression criteria are both met will be declared the P2RD and the study will proceed to phase 2.

  2. Overall Response Rates (ORR) to combination therapy [ Time Frame: 18 weeks - 2 years ]
    To determine whether addition of idelalisib to pembrolizumab in NSCLC improves ORR over that seen with pembrolizumab or other immune checkpoint inhibitors alone in treatment of NSCLC.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

All subjects must have documented metastatic or recurrent NSCLC from biopsy. They must have failed or progressed on platinum-based chemotherapy (e.g. cisplatin, carboplatin) as well as immune checkpoint inhibitor therapy (e.g nivolumab or pembrolizumab). Patients with EGFR/ALK mutations/translocations must have failed or progressed on small molecule inhibitor therapies (e.g. erlotinib, afatinib, etc.).

Inclusion Criteria:

  • Have at least one measurable lesion
  • Have an ECOG Performance Status of 1 or less
  • Demonstrate adequate organ function as defined in the protocol.
  • Female subjects of childbearing potential must have a negative pregnancy test before starting treatment; they must also be willing to use two methods of birth control or abstain from heterosexual activity for the duration of the study.
  • Male subjects must agree to use an adequate method of contraception starting with the first dose of study therapy through the duration of the study.

Exclusion Criteria:

  • Is currently receiving study drug in another trial; or has participated in an investigational drug study within 3 weeks of the first dose of treatment.
  • Is within 3 weeks of most recent chemotherapy.
  • Has a history of hypersensitivity to pembrolizumab or idelalisib, or any of their excipients.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated, stable, brain metastases may participate; carcinomatous meningitis is excluded regardless of clinical stability.
  • Has known history of non-infectious pneumonitis that required steroid use or has current pneumonitis.
  • Has a known history of active TB (Bacillus Tuberculosis)
  • Has active autoimmune disease that has required treatment; known history of Human Immunodeficiency Virus (HIV); known active Hepatitis B or Hepatitis C.
  • Has an active infection requiring systemic therapy.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03257722


Contacts
Layout table for location contacts
Contact: Lisa Marshall, MSN, RN, CNL 706-721-5095 LMarshall@augusta.edu
Contact: Carrie McAteer, BA, CCRC 706-721-1409 Cancer_Center_Trials@augusta.edu

Locations
Layout table for location information
United States, Georgia
Georgia Cancer Center at Augusta University Recruiting
Augusta, Georgia, United States, 30912
Sponsors and Collaborators
Zhonglin Hao
Merck Sharp & Dohme Corp.
Gilead Sciences
Investigators
Layout table for investigator information
Principal Investigator: Zhonglin Hao, MD, PhD Georgia Cancer Center

Layout table for additonal information
Responsible Party: Zhonglin Hao, Associate Professor of Medicine, Cancer Biology; Leader, Thoracic Oncology Program, Georgia Cancer Center, Augusta University
ClinicalTrials.gov Identifier: NCT03257722     History of Changes
Other Study ID Numbers: GCC-16053
First Posted: August 22, 2017    Key Record Dates
Last Update Posted: September 29, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Zhonglin Hao, Augusta University:
Non Small Cell Lung Cancer
Metastasis
Recurrence
Immunotherapy

Additional relevant MeSH terms:
Layout table for MeSH terms
Idelalisib
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasm Metastasis
Recurrence
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neoplastic Processes
Pathologic Processes
Disease Attributes
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action