Lung Cancer With Copanlisib and Durvalumab

Non Small Cell Lung Cancer Clinical Trial

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Official title:

Boosting Immune Response With Copanlisib in Locally Advanced Unresectable Non-Small Cell Lung Cancer Receiving Durvalumab, A Phase Ib Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04895579
• Other study ID #: MCC-20-LUN-119-PMC
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: May 12, 2021
• Est. completion date: June 2025

Study information

• Verified date: February 2024
• Source: University of Kentucky
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The current study focuses on unresectable stage III non-small cell lung cancer (NSCLC) patients who are starting Durvalumab consolidation after concurrent chemoradiation with a goal of cure. The overall hypothesis of this study is that the addition of Copanlisib to Durvalumab will be well-tolerated at a biweekly schedule. It will test whether the addition of Copanlisib to Durvalumab can overcome resistance to Durvalumab.

Description:

Treatment will be administered in outpatient settings. Durvalumab will be administered as infusion intravenously once every two weeks on D1 and D15, every 28 days (10 mg/Kg based on body weight) or 1500mg on D1 every 28 days. Copanlisib will be given as infusion intravenously on D1, D15 in a 28-day cycle (flat dose). The starting dose of Copalisib will be 60 mg D1 and D15. It will be reduced to 45 mg for the first dose reduction and to 30 mg for the second dose reduction. The Durvalumab dose will remain constant when Copanlisib is reduced.

Once the appropriate dose is determined, e.g. Copanlisib 60 mg iv d1, 15, q4w, in the dose-finding phase, this will become the recommended dose for the dose-expansion phase. Patients will be treated at the dose-expansion phase to increase our understanding of pharmacokinetics and to confirm safety as well as initial efficacy in this population.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 11
• Est. completion date: June 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed NSCLC (e.g., adenocarcinoma, squamous cell) deemed unresectable or inoperable who have received concurrent chemoradiation.

• Durvalumab will be started as consolidation therapy

• Have at least one measurable lesion.

• ECOG performance status =2.

• Adequate organ and marrow function.

• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Mixed Non-small cell and small cell histology; known EGFR and/or ALK driver mutations.

• Treated with sequential chemoradiation therapy.

• Autoimmune disease, such as rheumatoid arthritis, systemic lupus erythematosus, requiring systemic treatment with immunosuppressant in the past two years.

• Patients who are receiving any other investigational agents orally or intravenously.

• Systemic steroid for other purpose exceeding 10 mg prednisone a day except local injection at the discretion of the investigator.

• Solid organ or bone marrow transplant recipients.

• History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function.

• Patients with uncontrolled inter-current illness.

• Patients with psychiatric illness/social situations that would limit compliance with study requirements and patients with seizure disorder not well controlled.

• Received live vaccine in the past 4 weeks.

• Pregnant or breast-feeding/lactating women.

• Receiving medications prohibited by the study.

• New York Heart Association Class 3 or above.

• Myocardial infarction within the last 6 months.

• Unstable angina.

• Venous thromboembolism within last 3 months.

• Evidence or history of bleeding diathesis. Any hemorrhage or bleeding event = CTCAE Grade 3 within 4 weeks.

• Proteinuria of = CTCAE Grade 3 or estimated by urine protein: creatinine ratio > 3.5

• Major surgeries within the last 28 days.

• Any illness or medical conditions that are unstable or could jeopardize the safety of patients and their compliance in the study.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer

Intervention

Drug:
• Durvalumab
Durvalumab will be delivered at 10mg/kg via IV infusion at days 1 and 15 every 28 days or 1500 mg on D1, q4w.
• Copanlisib
Copanlisib will be delivered at various doses (30-60mg/kg) via IV infusion at days 1 and 15 every 28 days.

Locations

Country	Name	City	State
United States	Markey Cancer Center	Lexington	Kentucky

Sponsors (2)

Lead Sponsor	Collaborator
Zhonglin Hao	Bayer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicity	The number of dose limiting toxicities will be counted for each cohort.	28 days
Secondary	Objective Response Rate	The objective response rate is evaluated by iRECIST 1.1, which includes all patients with partial response (iPR) or complete response (iCR).	approximately 10 years
Secondary	Progression-Free Survival	Progression-free survival (PFS) is defined as the time interval between the date patients are started on Copanlisib treatment to the date of disease progression, death or last follow-up, whichever occurs first. Patients who are intolerant to treatment and removed from study by the principal investigator or withdraw from the study will be treated as censored data for the PFS analysis.	approximately 10 years
Secondary	Duration of Response	Duration of response (DOR) is defined as the time interval between the initial response to therapy and subsequent disease progression or relapse. Non-responders will be assigned a DOR equal to zero.	approximately 10 years