Lung Cancer With Copanlisib and Durvalumab (LCD)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: Durvalumab; Drug: Copanlisib

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yvonne Taul, RN; Phone Number: 859-323-2354; Email: yvonne.taul@uky.edu

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Markey Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Copanlisib (30-60mg iv); Patients in the group will receive Durvalumab at 10mg/kg (IV infusion on days 1 and 15, q28 days or 1500mg day 1 q28d). They will also receive Copanlisib ranging from 30mg to 60mg (IV infusion on days 1 and 15, q 28 days).	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.; Other Names: Imfinzi; Drug: Copanlisib; Copanlisib will be delivered at various doses (30-60mg/kg) via IV infusion at days 1 and 15 every 28 days.; Other Names: Aliqopa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicity	The number of dose limiting toxicities will be counted for each cohort.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Zhonglin Hao
• Collaborators: Bayer
• Investigators: Principal Investigator: Zhonglin Hao, MD, University of Kentucky

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2021
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: May 17, 2021
• First Submitted That Met QC Criteria: May 17, 2021
• First Posted (Actual): May 20, 2021

Study Record Updates

• Last Update Posted (Estimated): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Stage 3A, 3B; Chemoradiation therapy; Durvalumab consolidation/maintenance; Copanlisib
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab
• Other Study ID Numbers: MCC-20-LUN-119-PMC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No