Lung Cancer With Copanlisib and Durvalumab (LCD)

• ClinicalTrials.gov Identifier: NCT04895579
• Recruitment Status: Recruiting
• First Posted: May 20, 2021
• Last Update Posted: March 9, 2022
• Sponsor: Zhonglin Hao
• Collaborator: Bayer
• Information provided by (Responsible Party): Zhonglin Hao, University of Kentucky

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Non Small Cell Lung Cancer	Drug: Durvalumab; Drug: Copanlisib	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Dose finding cohort and dose expansion cohort up to 18 patients
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Boosting Immune Response With Copanlisib in Locally Advanced Unresectable Non-Small Cell Lung Cancer Receiving Durvalumab, A Phase Ib Study
• Actual Study Start Date: May 12, 2021
• Estimated Primary Completion Date: June 2031
• Estimated Study Completion Date: June 2031

Arms and Interventions

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 Name: 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 Name: Aliqopa

Outcome Measures

Primary Outcome Measures :

1. Dose Limiting Toxicity [ Time Frame: 28 days ]
   The number of dose limiting toxicities will be counted for each cohort.

Secondary Outcome Measures :

1. Objective Response Rate [ Time Frame: approximately 10 years ]
   The objective response rate is evaluated by iRECIST 1.1, which includes all patients with partial response (iPR) or complete response (iCR).
2. Progression-Free Survival [ Time Frame: approximately 10 years ]
   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.
3. Duration of Response [ Time Frame: approximately 10 years ]
   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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Yvonne Taul, RN; 859-323-2354; Yvonne.Taul@uky.edu

Locations

United States, Kentucky

Markey Cancer Center; Recruiting

Lexington, Kentucky, United States, 40536

Contact: Zhonglin Hao, MD 859-218-6704 zhonglin.hao@uky.edu

Sponsors and Collaborators

Zhonglin Hao

Bayer

Investigators

• Principal Investigator: Zhonglin Hao, MD; University of Kentucky

More Information

• Responsible Party: Zhonglin Hao, Professor, University of Kentucky
• ClinicalTrials.gov Identifier: NCT04895579
• Other Study ID Numbers: MCC-20-LUN-119-PMC
• First Posted: May 20, 2021
• Last Update Posted: March 9, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Zhonglin Hao, University of Kentucky:

Stage 3A, 3B; Chemoradiation therapy; Durvalumab consolidation/maintenance; Copanlisib

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Durvalumab; Antineoplastic Agents, Immunological; Antineoplastic Agents