Non Small Cell Lung CancerPhase 1/2PILNCT03257722
Pembrolizumab + Idelalisib for Lung Cancer Study
A Phase 1/2 study testing Pembrolizumab and Idelalisib in people with Non Small Cell Lung Cancer and Metastasis, run by Asha Nayak at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer, Metastasis, Recurrence
- What is being tested?
- Pembrolizumab and Idelalisib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Sep 2017to 25 Aug 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Georgia Cancer Center at Augusta University
Augusta, Georgia, 30912
About this 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
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.
Read the 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.
- Conditions
- Non Small Cell Lung Cancer, Metastasis, Recurrence
- Being tested
- Pembrolizumab, Idelalisib
- Keywords
- Non Small Cell Lung Cancer, Metastasis, Recurrence, Immunotherapy
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Neoplasm Metastasis, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Keytruda, MK-3475
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).
IdelalisibDrug
Also called Zydelig, GS-1101
Phosphatidylinositol 3-kinase (PI3K) inhibitor which promotes anti-tumor immune response. Administered orally (PO).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Pembrolizumab; Drug: Idelalisib |
| 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. Receives: Drug: Pembrolizumab; Drug: Idelalisib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: First 9 weeks at each dose level
Secondary outcomes (2)
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.
Measured: 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.
Measured: 18 weeks - 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2017
- Study start26 Sep 2017
- Primary completion15 Aug 2020
- Study completion25 Aug 2021
Why it stopped: The study was terminated due to poor accrual.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- 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)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Asha Nayak
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Gilead Sciences
- Responsible party
- Sponsor-investigator, Asha Nayak, Augusta University
- Investigators
- Zhonglin Hao, MD, PhD, Principal investigator, Georgia Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03257722
- Sponsor's protocol ID
- GCC-16053
- Acronym
- PIL
- Status last verified
- Jan 2024
- First submitted
- 16 Aug 2017
- Last updated
- 28 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03257722
- Acronym / sponsor ID
- PIL / GCC-16053
- Conditions
- Non Small Cell Lung Cancer, Metastasis, Recurrence
- Keywords
- Non Small Cell Lung Cancer, Metastasis, Recurrence, Immunotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated due to poor accrual.
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Asha NayakUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Gilead Sciences
- Study start
- 26 Sep 2017 (actual)
- Primary completion
- 15 Aug 2020 (actual)
- Study completion
- 25 Aug 2021 (actual)
- First posted
- 22 Aug 2017 (actual)
- Results
- Posted 28 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Phase 1 Dose Escalation | Experimental | Drug: Pembrolizumab, Drug: IdelalisibSequential 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. |
| Phase 2 Efficacy | Experimental | Drug: Pembrolizumab, Drug: IdelalisibAll 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: Keytruda, MK-3475Anti PD-1 immunotherapeutic agent, which blocks a protective mechanism on cancer cells to allow the immune system to destroy cancer cells. Administered intravenously (IV). | Drug | Phase 1 Dose Escalation, Phase 2 Efficacy |
| IdelalisibAlso: Zydelig, GS-1101Phosphatidylinositol 3-kinase (PI3K) inhibitor which promotes anti-tumor immune response. Administered orally (PO). | Drug | Phase 1 Dose Escalation, Phase 2 Efficacy |
Primary outcome
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.
2 secondary outcomes
Dose-Finding Assessment for Optimum Dose of Idelalisib in Combination With Pembrolizumab
Time frame: 18-27 weeks
Overall Response Rates (ORR) to Combination Therapy
Time frame: 18 weeks - 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zhonglin Hao, MD, PhD principal investigator
Georgia Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pembrolizumab and Idelalisib in people with Non Small Cell Lung Cancer and Metastasis, run by Asha Nayak at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose-Limiting Toxicity (DLT) Events as Assessed by CTCAE v4.03 (time frame: First 9 weeks at each dose level). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2024.