Pembrolizumab + Idelalisib for Lung Cancer Study

NCT03257722 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: GCC-16053
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Non Small Cell Lung Cancer; Metastasis; Recurrence

Keywords

Non Small Cell Lung Cancer; Metastasis; Recurrence; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• Dose-Finding Assessment for Optimum Dose of Idelalisib in Combination With Pembrolizumab

  18-27 weeks

• Overall Response Rates (ORR) to Combination Therapy

  18 weeks - 2 years

Study Arms (2)

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.

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.

Drug: Pembrolizumab; Drug: Idelalisib

Interventions

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).

Also known as: Keytruda, MK-3475

Phase 1 Dose Escalation; Phase 2 Efficacy

Idelalisib DRUG

Phosphatidylinositol 3-kinase (PI3K) inhibitor which promotes anti-tumor immune response. Administered orally (PO).

Also known as: Zydelig, GS-1101

Phase 1 Dose Escalation; Phase 2 Efficacy

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Asha Nayak: lead
• Merck Sharp & Dohme LLC: collaborator
• Gilead Sciences: collaborator

Study Sites (1)

Georgia Cancer Center at Augusta University

Augusta, Georgia, 30912, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Recurrence

Interventions

pembrolizumab; idelalisib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Results Point of Contact

• Title: Asha Nayak, MD
• Organization: Augusta University

anayak@augusta.edu

706-721-2505

Study Officials

• Zhonglin Hao, MD, PhD

  Georgia Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: 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.

Study Record Dates

• First Submitted: August 16, 2017
• First Posted: August 22, 2017
• Study Start: September 26, 2017
• Primary Completion: August 15, 2020
• Study Completion: August 25, 2021
• Last Updated: February 28, 2024
• Results First Posted: February 28, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)