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The study was terminated due to poor accrual.
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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
| Gilead Sciences | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1 Dose Escalation | Experimental | 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. |
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| Phase 2 Efficacy | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pembrolizumab | Drug | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose-Limiting Toxicity (DLT) Events as Assessed by CTCAE v4.03 | 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. | First 9 weeks at each dose level |
| Measure | Description | Time Frame |
|---|---|---|
| Dose-Finding Assessment for Optimum Dose of Idelalisib in Combination With Pembrolizumab | 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. |
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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:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Zhonglin Hao, MD, PhD | Georgia Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Georgia Cancer Center at Augusta University | Augusta | Georgia | 30912 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Phase 1 Dose Escalation 50mg | 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. Only two patients were dosed on this trial at 50mg. Two patients were screen fails. 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). Idelalisib: Phosphatidylinositol 3-kinase (PI3K) inhibitor which promotes anti-tumor immune response. Administered orally (PO). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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No patients were enrolled in Phase 2.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. Only two patients were dosed on this trial at 50mg. Two patients were screen fails. 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). Idelalisib: Phosphatidylinositol 3-kinase (PI3K) inhibitor which promotes anti-tumor immune response. Administered orally (PO). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Dose-Limiting Toxicity (DLT) Events as Assessed by CTCAE v4.03 | 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. | No patients were enrolled in Phase 2. | Posted | Count of Participants | Participants | First 9 weeks at each dose level |
|
Six months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Phase 1 Dose Escalation 50mg | 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. 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). Idelalisib: Phosphatidylinositol 3-kinase (PI3K) inhibitor which promotes anti-tumor immune response. Administered orally (PO). |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Asha Nayak, MD | Augusta University | 706-721-2505 | anayak@augusta.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Dec 5, 2017 | Jul 31, 2023 | Prot_SAP_ICF_000.pdf |
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| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D009362 | Neoplasm Metastasis |
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
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| ID | Term |
|---|---|
| C582435 | pembrolizumab |
| C552946 | idelalisib |
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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.
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| Idelalisib | Drug | Phosphatidylinositol 3-kinase (PI3K) inhibitor which promotes anti-tumor immune response. Administered orally (PO). |
|
|
| 18-27 weeks |
| Overall Response Rates (ORR) to Combination Therapy | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | 18 weeks - 2 years |
| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Secondary | Dose-Finding Assessment for Optimum Dose of Idelalisib in Combination With Pembrolizumab | 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. | Trial did not progress past Phase 1. | Posted | Number | mg | 18-27 weeks |
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|
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| Secondary | Overall Response Rates (ORR) to Combination Therapy | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | No patients were enrolled in Phase 2. | Posted | Count of Participants | Participants | 18 weeks - 2 years |
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| 0 |
| 2 |
| 0 |
| 2 |
| 0 |
| 2 |
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| D013899 |
| Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D020969 | Disease Attributes |