Abequolixron (RGX-104) and Durvalumab in Lung Cancer

A Pilot Window of Opportunity Study Evaluating Durvalumab (MEDI4736) in Combination With Platinum Doublet Chemotherapy Followed by Evaluation of Durvalumab (MEDI4736) in Combination With Platinum Doublet Chemotherapy and Abequolixron (RGX-104) in Non-small Cell Lung Cancer

Non-Small Cell Lung Cancer (NSCLC) is one of the deadliest types of cancer. In lung cancer patients with a tumor that can be removed by surgery, adjuvant chemotherapy increases survival. Neoadjuvant therapy may have advantages such as, it may be more tolerable prior to surgery, earlier treatment may be more efficacious, and it can provide an indication of treatment response. Neoadjuvant treatment can provide pre- and post-treatment specimens for correlative analysis to better understand mechanisms of action and resistance.

This pilot study will investigate the effects of neoadjuvant durvalumab plus platinum doublet chemotherapy and neoadjuvant durvalumab plus platinum doublet chemotherapy in combination with abequolixron (RGX-104), an LXR/ApoE agonist, in subjects with NSCLC who are scheduled to undergo surgical resection as part of their standard of care.

The purpose of this study is to study how well using a combination of durvalumab, platinum doublet chemotherapy (carboplatin/abraxane or carboplatin/pemetrexed), and abequolixron treats non-small cell lung cancer before surgery. Durvalumab (a type of immunotherapy) and platinum doublet chemotherapy are drugs that are individually approved for use during the treatment of cancer. FDA (Food and Drug Administration) has not approved the combined use of these drugs in treating non-small cell lung cancer. Abequolixron is not FDA approved for the treatment of cancer.

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Durvalumab; Drug: Carboplatin; Drug: Abequolixron; Drug: Abraxane; Drug: Pemetrexed

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lauren Higgins; Phone Number: 919-966-4432; Email: lqhiggin@ad.unc.edu
• Study Contact Backup: Name: Lori Stravers; Email: lori_stravers@med.unc.edu

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Not yet recruiting
      • Moffitt Cancer Center
      • Contact: Tara Ackerman; Email: tara.ackerman@moffitt.org
      • Principal Investigator: Alberto Chiaporri, MD
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27516
      • Recruiting
      • UNC Lineberger Comprehensive Cancer Center
      • Principal Investigator: Jared Weiss, MD
      • Contact: Lauren Higgins; Email: lqhiggin@ad.unc.edu
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Not yet recruiting
      • Fox Chase Cancer Center
      • Contact: Michael Oldfield; Email: Michael.Oldfield@fccc.edu
      • Principal Investigator: Hossein Borghaei, MS, DO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Willing and able to provide written informed consent obtained to participate in the study and

   HIPAA authorization for the release of personal health information.

2. Age ≥ 18 years at the time of consent.

3. Histologically or cytologically confirmed non-small cell lung cancer for which surgical resection

   would be standard of care.

4. ECOG Performance Status of 0-1
5. Body weight of > 40 kg
6. Is able to swallow and retain oral medication.

Exclusion Criteria:

1. Participation in another clinical study with an investigational product during the last 3 weeks

2. Concurrent enrollment in another clinical study unless it is an observational (non-interventional)

   clinical study or during the follow-up period of an interventional study.

3. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment with the

   exception of those mentioned in this protocol. Concurrent use of hormonal therapy for noncancer-

   related conditions (e.g., hormone replacement therapy) is acceptable.

4. Lack of full recovery from a major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP.
5. History of allogenic organ transplantation.

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: Neoadjuvant therapy; Subjects with operable Non-Small Cell Lung Cancer received neoadjuvant durvalumab plus platinum doublet chemotherapy and neoadjuvant durvalumab plus platinum doublet chemotherapy in combination with abequolixron (RGX-104), an LXR/ApoE agonist.

Drug: Durvalumab; 1,500 mg Durvalumab IV infusion will be given on day 1 of each cycle for 3 cycles.; Other Names: Imfinzi; Drug: Carboplatin; Carboplatin IV infusion will be given on day 1 of each cycle for 3 cycles. The dose will be AUC 5.; Other Names: Paraplatin; Drug: Abequolixron; 100 or 120 mg Abequolixron will be administered by mouth twice a day for 5 days followed by 2 days off throughout your treatment (5 days a week for up to 9 weeks).; Other Names: RGX 104; RGX-104; RGX104; SB-742881; Drug: Abraxane; 100 mg/m2 Abraxane will be given by IV infusion on days 1, 8, and 15 of each cycle for 3 cycles.; Other Names: Nab-paclitaxel; Paclitaxel albumin-bound; Drug: Pemetrexed; 500 mg/m2 pemetrexed will be given by IV infusion on day 1 of each cycle for 3 cycles.; Other Names: Alimta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of surgery	Feasibility will be evaluated as the delay time between the completion of neoadjuvant therapy and surgery. A failure of feasibility will be defined as a delay in the planned surgery of more than 42 days (surgical delay of 35 days, plus 7 days for scheduling).	Up to 120 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicities	Toxicities related to study treatment therapy will be classified and graded according to The NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0). NCI-CTCAE v5.0 is a descriptive terminology that can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.	Up to 1 years after surgery
Major pathologic response rate - squamous histology	Major pathologic complete response rate after neoadjuvant chemotherapy will be assessed via surgical pathology report in subjects with non-small cell lung carcinoma - squamous histology. Major pathologic response is defined as equal to or less than 10% residual tumor following neoadjuvant therapy.	Up to 120 days
Major pathologic response rate - non squamous histology	Major pathologic complete response rate after neoadjuvant chemotherapy will be assessed via surgical pathology report in subjects with non-small cell lung carcinoma - nonsquamous histology. Major pathologic response is defined as equal to or less than 10% residual tumor following neoadjuvant therapy.	Up to 120 days
Pathologic complete response rate (PCR) -durvalumab in combination with platinum doublet chemotherapy	PCR -durvalumab in combination with platinum doublet chemotherapy will be histologically evaluated at the time of surgery, in subjects receiving neoadjuvant treatment with durvalumab in combination with platinum doublet chemotherapy. Pathologic complete response (pCR) is the disappearance of all signs of cancer in tissue samples removed during surgery or biopsy (pT0). Also called pathologic complete remission. Pathologic Partial Response (pPR), is the presence of only non-invasive cancer in tissue samples (<pT2)	Up to 120 days
Pathologic complete response rate (PCR) - durvalumab in combination with platinum doublet chemotherapy plus abequolixron	Pathologic complete response rate (PCR) - durvalumab in combination with platinum doublet chemotherapy plus abequolixron will be histologically evaluated at the time of surgery, in subjects receiving neoadjuvant treatment with durvalumab in combination with platinum doublet chemotherapy plus abequolixron. Pathologic complete response (pCR) is the disappearance of all signs of cancer in tissue samples removed during surgery or biopsy (pT0). Also called pathologic complete remission. Pathologic Partial Response (pPR), is the presence of only non-invasive cancer in tissue samples (<pT2)	Up to 120 days
Clinical response rate (CRR) - durvalumab in combination with platinum doublet chemotherapy	CRR is defined as the clinical response rate is the combination of complete response (CR) + partial response (PR) defined by The overall response rate will be assessed per Response Evaluation Criteria Solid Tumors (RECIST) 1.1 in subjects receiving durvalumab in combination with platinum doublet chemotherapy. Based on RECIST v1.1, Complete Response (CR) is the Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Overall Response Rate (ORR) = CR + PR/total number of subjects.	Up to 1 years after surgery
Clinical response rate (CRR) - durvalumab in combination with platinum doublet chemotherapy plus abequolixron	CRR is defined as the clinical response rate is the combination of complete response (CR) + partial response (PR) defined by The overall response rate will be assessed per Response Evaluation Criteria Solid Tumors (RECIST) 1.1 in subjects receiving durvalumab in combination with platinum doublet chemotherapy plus abequolixron. Based on RECIST v1.1, Complete Response (CR) is the Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Overall Response Rate (ORR) = CR + PR/total number of subjects.	Up to 1 years after surgery
Recurrence-free survival (RFS) - durvalumab in combination with platinum doublet chemotherapy	RFS - durvalumab in combination with platinum doublet chemotherapy will be defined as the time from the time after surgery to disease recurrence or death (whichever occurs first) and will be defined by RECIST 1.1. in subjects receiving neoadjuvant therapy with durvalumab in combination with platinum doublet chemotherapy. Based on RECIST v1.1 Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	Up to 5 years
Recurrence-free survival (RFS)- durvalumab in combination with platinum doublet chemotherapy plus abequolixron	RFS - durvalumab in combination with platinum doublet chemotherapy will be defined as the time from the time after surgery to disease recurrence or death (whichever occurs first) and will be defined by RECIST 1.1. in subjects receiving neoadjuvant therapy with durvalumab in combination with platinum doublet chemotherapy plus abequolixron Based on RECIST v1.1 Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	Up to 5 years
Overall Survival (OS) - durvalumab	OS - durvalumab is defined as the time from the first day of study therapy to the date of death for any cause, in subjects receiving neoadjuvant therapy with durvalumab in combination with platinum doublet chemotherapy.	Up to 5 years
Overall Survival (OS) - durvalumab in combination with platinum doublet chemotherapy plus abequolixron	OS - durvalumab in combination with platinum doublet chemotherapy plus abequolixron is defined as the time from the first day of study therapy to date of death for any cause, in subjects receiving neoadjuvant therapy with durvalumab in combination with platinum doublet chemotherapy plus abequolixron.	Up to 5 years

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborators: AstraZeneca; Rgenix, Inc.
• Investigators: Principal Investigator: Jared Weiss, MD, UNC Lineberger Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• Clinical trials at UNC Lineberger

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2024
• Primary Completion (Estimated): December 19, 2024
• Study Completion (Estimated): December 19, 2024

Study Registration Dates

• First Submitted: June 9, 2023
• First Submitted That Met QC Criteria: June 9, 2023
• First Posted (Actual): June 22, 2023

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: carboplatin; Neoadjuvant therapy; abraxane; pemetrexed; abequolixron (RGX-104); LXR/ApoE
• 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; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Folic Acid Antagonists; Carboplatin; Paclitaxel; Durvalumab; Albumin-Bound Paclitaxel; Pemetrexed
• Other Study ID Numbers: LCCC2113

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