Abequolixron (RGX-104) and Durvalumab in Lung Cancer

• ClinicalTrials.gov Identifier: NCT05911308
• Recruitment Status: Recruiting
• First Posted: June 22, 2023
• Last Update Posted: April 22, 2024
• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborators: AstraZeneca; Rgenix, Inc.
• Information provided by (Responsible Party): UNC Lineberger Comprehensive Cancer Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Non-Small Cell Lung Cancer	Drug: Durvalumab; Drug: Carboplatin; Drug: Abequolixron; Drug: Abraxane; Drug: Pemetrexed	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: April 1, 2024
• Estimated Primary Completion Date: December 19, 2024
• Estimated Study Completion Date: December 19, 2024

Arms and Interventions

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 Name: 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 Name: 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: Paclitaxel albumin-bound; Nab-paclitaxel; Drug: Pemetrexed; 500 mg/m2 pemetrexed will be given by IV infusion on day 1 of each cycle for 3 cycles.; Other Name: Alimta

Outcome Measures

Primary Outcome Measures :

1. Feasibility of surgery [ Time Frame: Up to 120 days ]
   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).

Secondary Outcome Measures :

1. Toxicities [ Time Frame: Up to 1 years after surgery ]

   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.

2. Major pathologic response rate - squamous histology [ Time Frame: Up to 120 days ]

   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.

3. Major pathologic response rate - non squamous histology [ Time Frame: Up to 120 days ]

   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.

4. Pathologic complete response rate (PCR) -durvalumab in combination with platinum doublet chemotherapy [ Time Frame: Up to 120 days ]

   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)

5. Pathologic complete response rate (PCR) - durvalumab in combination with platinum doublet chemotherapy plus abequolixron [ Time Frame: Up to 120 days ]

   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)

6. Clinical response rate (CRR) - durvalumab in combination with platinum doublet chemotherapy [ Time Frame: Up to 1 years after surgery ]

   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.

7. Clinical response rate (CRR) - durvalumab in combination with platinum doublet chemotherapy plus abequolixron [ Time Frame: Up to 1 years after surgery ]

   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.

8. Recurrence-free survival (RFS) - durvalumab in combination with platinum doublet chemotherapy [ Time Frame: Up to 5 years ]

   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.

9. Recurrence-free survival (RFS)- durvalumab in combination with platinum doublet chemotherapy plus abequolixron [ Time Frame: Up to 5 years ]

   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.

10. Overall Survival (OS) - durvalumab [ Time Frame: Up to 5 years ]
    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.
11. Overall Survival (OS) - durvalumab in combination with platinum doublet chemotherapy plus abequolixron [ Time Frame: Up to 5 years ]
    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.

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:

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.

Contacts and Locations

Contacts

Contact: Lauren Higgins; 919-966-4432; lqhiggin@ad.unc.edu

Contact: Lori Stravers; lori_stravers@med.unc.edu

Locations

United States, Florida

Moffitt Cancer Center; Not yet recruiting

Tampa, Florida, United States, 33612

Contact: Tara Ackerman tara.ackerman@moffitt.org

Principal Investigator: Alberto Chiaporri, MD

United States, North Carolina

UNC Lineberger Comprehensive Cancer Center; Recruiting

Chapel Hill, North Carolina, United States, 27516

Contact: Lauren Higgins lqhiggin@ad.unc.edu

Principal Investigator: Jared Weiss, MD

United States, Pennsylvania

Fox Chase Cancer Center; Not yet recruiting

Philadelphia, Pennsylvania, United States, 19111

Contact: Michael Oldfield Michael.Oldfield@fccc.edu

Principal Investigator: Hossein Borghaei, MS, DO

Sponsors and Collaborators

UNC Lineberger Comprehensive Cancer Center

AstraZeneca

Rgenix, Inc.

Investigators

• Principal Investigator: Jared Weiss, MD; UNC Lineberger Comprehensive Cancer Center

More Information

Additional Information:

Clinical trials at UNC Lineberger 

• Responsible Party: UNC Lineberger Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT05911308
• Other Study ID Numbers: LCCC2113
• First Posted: June 22, 2023
• Last Update Posted: April 22, 2024
• Last Verified: April 2024

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 UNC Lineberger Comprehensive Cancer Center:

Neoadjuvant therapy; abequolixron (RGX-104); LXR/ApoE; carboplatin; abraxane; pemetrexed

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; Paclitaxel; Albumin-Bound Paclitaxel; Carboplatin; Pemetrexed; Durvalumab; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Antineoplastic Agents, Immunological