Clinical trial NCT05001282: A Study to Evaluate ELU001 in Patients With Solid Tumors That Overexpress Folate Receptor Alpha (FRα)
Official title: Dose Escalation and Expansion Clinical Study to Evaluate the Safety and Efficacy of ELU001 in Subjects Who Have Advanced, Recurrent or Refractory FRα Overexpressing Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Ovarian Cancer
Ovarian Neoplasms
Ovarian Carcinoma
Endometrial Cancer
Ovary Cancer
Ovary Neoplasm
Ovary Disease
Ovary Metastasis
Ovarian Diseases
Ovarian Cancer Stage
Ovarian Epithelial Cancer
Ovarian Adenocarcinoma
Ovarian Serous Adenocarcinoma
Ovarian Neoplasm Epithelial
Ovarian Cancer Recurrent
Endometrial Diseases
Endometrial Adenocarcinoma
Endometrial Carcinosarcoma
Endometrial Clear Cell Adenocarcinoma
Endometrioid Adenocarcinoma
Endometrial Neoplasms
Endometrial Cancer Recurrent
Endometrioid Tumor
Fallopian Tube Cancer
Peritoneal Cancer
Keywords: Folate Receptor Alpha
Carcinomas
Recurrent, Refractory
Folate Receptor alpha moderate expression
Folate Receptor alpha high expression
ELU001
Exatecan
C'Dot
C-Dot
Folic Acid
Payload
Nanoparticle
C'Dot drug conjugate
CDC
Linker
ELU-FRa-1
FOLR1
Lead sponsor: Elucida Oncology
Sponsor class: INDUSTRY
First posted: 2021-08-11
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Dose Escalation Dose Expansion, Simon's 2-stage
Primary purpose: TREATMENT

Brief summary: This study, ELU- FRα-1, was focused on adult subjects who have advanced, recurrent or refractory folate receptor alpha (FRα) overexpressing tumors considered to be topoisomerase 1 inhibitor-sensitive based on scientific literature, and, in the opinion of the Investigator, have no other meaningful life-prolonging therapy options available.

Detailed description: The study had two parts: Part 1 Dose Escalation Safety Study to identify the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D), and Part 2 Tumor Group Expansion Cohort(s) where specific cancer types will be evaluated for efficacy and safety at the RP2D.

Part 1, subjects with cancer types with a high likelihood of having FRα overexpressing tumors based on historical data, specifically, ovarian, endometrial, colorectal, gastric, gastroesophageal junction, triple negative breast, or non-small cell lung cancers, or cholangiocarcinoma, will be enrolled in a basket clinical study. Retrospective analysis of folate receptor alpha (FRα) expression status will be determined. Part 1 is currently closed for further recruitment.

Part 2 Stage 1 of a Simon's Two-Stage design, tumor group expansion cohorts, each consisting of subjects with cancer types studied as part of the basket in Part 1. Part 2 is closed for recruitment.

Eligibility criteria: Key Inclusion Criteria:

Patients must meet the following criteria to enroll in this study:

* Part 1 Documented diagnosis of ovarian cancer, endometrial cancer, colorectal cancer, gastric cancer, gastroesophageal junction cancer, triple negative breast cancer, non-small cell lung cancer, or cholangiocarcinoma
* Part 2 Ovarian Cancer or Endometrial Cancer
* No other meaningful life-prolonging therapy option available
* Must provide archival tumor tissue or a newly obtained tumor biopsy specimen prior to the first dose of ELU001 for folate receptor alpha (FRα) expression analysis. Previous FRα expression test results may be used in certain circumstances
* Adequate organ function
* Measurable disease, or in the absence of measurable disease, non-measurable disease as per Response evaluation criteria in solid tumors (RECIST) v1.1
* Part 1: Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2; Part 2: ECOG performance status of 0 or 1.
* Recovered from previous surgeries
* Agree to highly effective contraception, not to get pregnant, or for men, not father a child during study participation

Key Exclusion Criteria:

Patients who meet any of the following are not eligible to enroll in this study:

* Clinically significant eye disorders
* Taken any treatments that use the protein folate receptor alpha or FRα to work
* Taken any other experimental treatments
* History of significant cardiac issues or other cancers within 3 years.
* Significant anemia, significant neutropenia, or significant thrombocytopenia (e.g., not enough platelets in your blood - platelets held stop bleeding in your body)
* Detectable viral load for HIV (human immunodeficiency virus), hepatitis B or C.
* If you are pregnant.
* Part 1: Cannot have active autoimmune diseases such as rheumatoid arthritis, SLE (systemic lupus erythematosus), ulcerative colitis, Crohn's Disease, MS (multiple sclerosis), ankylosing spondylitis, thyroiditis that require treatments that suppress your immune system.
* Part 1: if your cancer has spread to your brain.
* Part 2: You can have cancer that has spread to your brain but there are exceptions. The cancer in your brain cannot be causing any symptoms, it cannot be larger than 3 cm, there can be no evidence on a scan that shows your brain tissue has shifted from its expected position inside the skull (called "herniation") or be bleeding in the skull or brain itself (called "hemorrhage").

Primary outcomes:
measure: Part 1 Dose Escalation: The Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of ELU001 for IV infusion in patients with over-expressing Folate Receptor Alpha tumors.
timeFrame: 28 days
measure: Part 2 Dose Expansion: To determine overall response rate (ORR) (complete response [CR] + partial response [PR]) of ELU001 for IV infusion in patients with over-expressing Folate Receptor Alpha tumors, per RECIST v1.1.
timeFrame: First dose of study drug until responses of CR or PR, assessed up to 12 months.
Secondary outcomes:
measure: Part 1 Dose Escalation: To determine overall response rate (ORR) (complete response [CR] + partial response [PR]) of ELU001 for IV infusion in patients with over-expressing Folate Receptor Alpha tumors, per RECIST v1.1.
timeFrame: First dose of study drug until responses of CR or PR, assessed up to 12 months.
measure: Part 1 and Part 2: To determine Duration of Response (DOR) of ELU001 for IV infusion in patients with over-expressing Folate Receptor Alpha tumors.
timeFrame: Date of first response (CR or PR) until the date of disease progression or up to 12 months, whichever occurs first.
measure: Part 1 and Part 2: Number of participants with adverse events as assessed by CTCAE v5.0 Safety Evaluations.
timeFrame: First dose of study drug up to 28 days after the last dose of study drug or up to 12 months, whichever occurs first.
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic - Phoenix, AZ
state: Arizona
city: Fullerton
country: United States
facility: Providence Medical Foundation
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville, FL
state: Florida
city: Margate
country: United States
facility: D&H Cancer Research Center
state: Florida
city: Orlando
country: United States
facility: Sarah Cannon Research Institute at Florida Cancer Specialists
state: Florida
city: Hinsdale
country: United States
facility: Hope and Healing Cancer Services
state: Illinois
city: Peoria
country: United States
facility: OSF Saint Francis Medical Center
state: Illinois
city: Rochester
country: United States
facility: Mayo Clinic - Rochester, MN
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center - Duke Cancer Institute
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University, Sidney Kimmel Cancer Center
state: Pennsylvania
city: Providence
country: United States
facility: Women & Infants Hospital of Rhode Island
state: Rhode Island
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Nashville
country: United States
facility: Sarah Cannon Research Institute at Tennessee Oncology
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: San Antonio
country: United States
facility: New Experimental Therapeutics of San Antonio (NEXT Oncology)
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
Study officials:
References: