A Study of RGX-104 in Patients With Advanced Lung & Endometrial Cancer

Completed · Phase 1

Conditions studied: Endometrial Cancer, Endometrial Cancer Recurrent, Lung Cancer Recurrent, Lung Cancer, Non-small Cell Lung Cancer Metastatic, Non-small Cell Carcinoma

In brief

Study RGX-104-001 is a Phase 1, first-in-human, dose escalation and expansion study of RGX-104, an oral small molecule targeting the liver X receptor (LXR), as a single agent and in combination with nivolumab, ipilimumab, docetaxel, or pembrolizumab plus carboplatin/pemetrexed.

Key facts

Study ID

NCT02922764

Run by

Inspirna, Inc.

People needed

146

Starts

2016-11-01

Expected to finish

2025-01-22

Last updated by the study team

2025-03-26

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• The patient must have histologic or cytologic evidence of a malignant solid tumor or lymphoma (any histology) and must have advanced disease, defined as cancer that is either metastatic or locally advanced and unresectable (and for which additional radiation therapy or other locoregional therapies are not considered feasible).
• With the exception of dose escalation with pembrolizumab plus carboplatin/pemetrexed, patients enrolled in the dose escalation stages must have disease that is resistant to or relapsed following available standard systemic therapy, or for which there is no standard systemic therapy or reasonable therapy in the physician's judgment likely to result in clinical benefit or if such therapy has been refused by the patient. Documentation of the reason must be provided for patients who have not received a standard therapy likely to result in clinical benefit.
• Patients enrolled in the expansion stages: Optional tumor biopsy may be obtained during the screening period and toward the beginning of Cycle 2 or at the time of PD, if earlier. If a biopsy is deemed by the investigator to not be in the patient's best interest, prior approval must be obtained from the Medical Monitor to waive this requirement.
• The patient must have disease that is measurable by standard imaging techniques per RECIST or immune-related response criteria (irRC; all tumor types except lymphoma) or International Working Group (IWG) revised response criteria for malignant lymphoma (lymphoma only). For patients with prior radiation therapy, measurable lesions must be outside of any prior radiation field(s), unless disease progression has been documented at that disease site subsequent to radiation.
• The patient is ≥18 years old.
• The patient has an ECOG PS of ≤1.
• The patient has adequate baseline organ function, as demonstrated by the following:
• Serum creatinine ≤1.5 × institutional upper limit of normal (ULN) or calculated creatinine clearance >30 mL/min (>45 ml/min for patients receiving carboplatin/pemetrexed).
• Serum albumin ≥2.5 g/dl;
• Bilirubin ≤1.5 × institutional ULN.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × institutional ULN. Patients enrolled in an expansion stage may have ALT and AST < 5 × institutional ULN if the patient has hepatic metastases;
• For patients not taking warfarin or other oral anticoagulants: international normalized ratio (INR) ≤1.5 or prothrombin time (PT) ≤1.5 × ULN; and either partial thromboplastin time or activated partial thromboplastin time (PTT or aPTT) ≤1.5 × ULN. Patients taking warfarin should be on a stable dose that results in a stable INR <3.5. Among patients receiving other oral anticoagulant therapy, PT or aPTT must be within the intended therapeutic range of the anticoagulant.
• The patient has adequate baseline hematologic function, as demonstrated by the following:
• Absolute neutrophil count (ANC) ≥1.5×109/L;
• Hemoglobin ≥8 g/dL and no red blood cell (RBC) transfusions during the prior 14 days;
• Platelet count ≥100×109/L and no platelet transfusions during the prior 14 days.
• The patient has a normal left ventricular ejection fraction (LVEF) per institutional criteria as determined by either echocardiography (ECHO) or multigated acquisition (MUGA) scanning.
• If the patient is a woman of child-bearing potential (WOCBP), she has had a negative serum or urine pregnancy test within 2 weeks prior to treatment.
• The patient (men and WOCBP) agrees to use acceptable contraceptive methods for the duration of time on the study, and continue to use acceptable contraceptive methods for 1 month after the last dose of study therapy. Patients receiving combination therapy must agree to use acceptable contraceptive methods for the duration of time on the study and continue to use acceptable contraceptive methods for 6 months after the last dose of study therapy.
• The patient has signed informed consent prior to initiation of any study-specific procedures or treatment.
• The patient is able to adhere to the study visit schedule and other protocol requirements, including follow-up for survival assessment.
• Tumor tissue (a minimum of 10 and up to 15 unstained slides, or paraffin block, ideally from the patient's most recent biopsy, must be made available prior to the first dose of study therapy.
• For patients with endometrial cancer enrolled in the ipilimumab combination expansion stage:
• The patient has Stage III, Stage IV, or recurrent, histologically-confirmed endometrial carcinoma with disease that is measurable per RECIST 1.1.
• The patient may have received up to THREE lines of prior therapy:

You may not qualify if…

• The patient has persistent clinically significant toxicities (Grade ≥2) from previous anticancer therapy (excluding Grade 2 chemotherapy-related neuropathy and alopecia which are permitted). Prior toxicities that resulted in laboratory abnormalities should have resolved to Grade ≤1, unless a higher-grade abnormality is allowed by the inclusion criteria. If medical therapy is required for the treatment of a laboratory abnormality, the dose and laboratory value(s) should be stable.
• If considered for combination therapy with nivolumab or ipilimumab, the patient has:
• Uncontrolled clinically significant pulmonary disease.
• A history of any grade immune-related ocular event.
• A history of Grade ≥3 immune-related adverse event regardless of offending agent.
• Active autoimmune disease that required systemic treatment in the past. Patients who have not required systemic treatment for at least two years may be enrolled if permission is provided after discussion with the Medical Monitor (replacement therapy, e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, is not considered a form of systemic treatment, and is allowed).
• Evidence of active noninfectious pneumonitis or history of interstitial lung disease.
• A risk of reactivation of hepatitis B or C.
• Previously received an immune therapy that was discontinued due to immune-related AEs, regardless of grade.
• Uncontrolled endocrine disorder. Patients who are on endocrine replacement therapy must be on a stable dose.
• The patient has received treatment with chemotherapy, external-beam radiation, or other systemic anticancer therapy within 14 days prior to study therapy administration (42 days for prior nitrosourea or mitomycin-C; patients with advanced prostate cancer who are receiving luteinizing hormone releasing hormone (LHRH) agonists are permitted onto the study and should continue use of these agents during study treatment).
• The patient has received treatment with an investigational systemic anticancer agent within 14 days prior to study therapy administration.
• The patient has previously received treatment with RGX-104 or another investigational agent that is a known LXR agonist.
• The patient has an additional active malignancy that may confound the assessment of the study endpoints. Patients with a past cancer history with substantial potential for recurrence must be discussed with the Medical Monitor before study entry. Patients with the following concomitant neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ (including transitional cell carcinoma, cervical intraepithelial neoplasia, and melanoma in situ), organ-confined prostate cancer with no evidence of progressive disease.
• The patient has clinically significant cardiovascular disease (e.g., uncontrolled or any New York Heart Association Class 3 or 4 heart failure (see Appendix 1), uncontrolled angina, history of myocardial infarction, unstable angina or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication).
• The patient has uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that in the opinion of the Investigator would put the patient at significant risk for pulmonary complications during the study.
• The patient has known active or suspected brain or leptomeningeal metastases. Central Nervous System (CNS) imaging is not required prior to study entry unless there is a clinical suspicion of CNS involvement. Patients with stable, treated brain metastases are eligible provided there is no evidence of CNS disease growth on imaging for at least 8 weeks following radiation therapy or other locoregional ablative therapy to the CNS.
• The patient has a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to study therapy administration. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.
• The patient has uncontrolled intercurrent illness including, but not limited to, uncontrolled infection requiring therapy, disseminated intravascular coagulation, or psychiatric illness/social situations that would limit compliance with study requirements.
• The patient is pregnant or breast feeding.
• The patient has known positive status for human immunodeficiency virus or active or chronic Hepatitis B or Hepatitis C.
• The patient is oxygen-dependent.
• The patient has a history of pancreatitis.
• The patient has Grade ≥2 hypercholesterolemia (total cholesterol >300 mg/dL or >7.75 mmol/L) and/or hypertriglyceridemia (triglyceride >300 mg/dL or >3.42 mmol/L) in the fasting state.
• QTcF >450 msec (males) or >470 msec (females).

Where it is running

• Arizona Oncology — Tucson, Arizona, United States
• Cedars-Sinai Medical Center — Los Angeles, California, United States
• University of Colorado — Aurora, Colorado, United States
• Rocky Mountain Cancer Centers — Denver, Colorado, United States
• Sarah Cannon Research Institute — Denver, Colorado, United States
• Florida Cancer Specialist — Lake Mary, Florida, United States
• Comprehensive Hematology Oncology — St. Petersburg, Florida, United States
• James Graham Brown Cancer Center — Louisville, Kentucky, United States
• Ochsner Clinic Foundation — New Orleans, Louisiana, United States
• Maryland Oncology — Columbia, Maryland, United States
• Regions Hospital — Saint Paul, Minnesota, United States
• Dartmouth Hitchcock Medical — Lebanon, New Hampshire, United States
• CINJ — New Brunswick, New Jersey, United States
• Quantum Santa Fe — Santa Fe, New Mexico, United States
• Columbia University Medical Center — New York, New York, United States
• OU Health Stephenson Cancer Center — Oklahoma City, Oklahoma, United States
• Oregon Health Sciences University — Portland, Oregon, United States
• Thomas Jefferson University Hospital — Philadelphia, Pennsylvania, United States
• Fox Chase Cancer Center — Philadelphia, Pennsylvania, United States
• The Sarah Cannon Research Institute — Nashville, Tennessee, United States
• Virginia Cancer Specialists, PC — Fairfax, Virginia, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.