Clinical trial NCT03257722: Pembrolizumab + Idelalisib for Lung Cancer Study
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Non Small Cell Lung Cancer
Metastasis
Recurrence
Keywords: Non Small Cell Lung Cancer
Metastasis
Recurrence
Immunotherapy
Lead sponsor: Augusta University
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
name: Gilead Sciences
First posted: 2017-08-22
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Number of Participants With Dose-Limiting Toxicity (DLT) Events as Assessed by CTCAE v4.03
timeFrame: First 9 weeks at each dose level
Secondary outcomes:
measure: Dose-Finding Assessment for Optimum Dose of Idelalisib in Combination With Pembrolizumab
timeFrame: 18-27 weeks
measure: Overall Response Rates (ORR) to Combination Therapy
timeFrame: 18 weeks - 2 years
Other outcomes:
Locations:
city: Augusta
country: United States
facility: Georgia Cancer Center at Augusta University
state: Georgia
Study officials:
affiliation: Georgia Cancer Center
name: Zhonglin Hao, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: