A Study to Evaluate ELU001 in Patients With Solid Tumors That Overexpress Folate Receptor Alpha (FRα)

Sponsor

Elucida Oncology (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05001282

Collaborator

(none)

166

Enrollment

Locations

Arm

Anticipated Duration (Months)

18.4

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study, ELU- FRα-1, is 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.

ELU001 is a new chemical entity described as a C'Dot drug conjugate (CDC), consisting of payloads (exatecans) and targeting moieties (folic acid analogs) covalently bound by linkers to the C'Dot particle carrier. ELU001 will be the first drug-conjugate of its kind to be introduced into the clinic, a first in class, and a novel molecular entity.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer Ovarian Neoplasms Ovarian Carcinoma Endometrial Cancer Colorectal Cancer Gastric Cancer Gastroesophageal Junction Adenocarcinoma Gastric Adenocarcinoma TNBC - Triple-Negative Breast Cancer Triple Negative Breast Cancer Cholangiocarcinoma Bile Duct Cancer Colon Cancer Colon Cancer Stage Colon Neoplasm Colon Adenocarcinoma Colon Rectal Cancer Colon Cancer Liver Metastasis Colorectal Neoplasms Colorectal Carcinoma Colorectal Adenocarcinoma Colorectal Cancer Metastatic Colorectal Cancer Stage IV Rectum Cancer Rectum Neoplasm Rectum Carcinoma Rectal Cancer Rectal Neoplasms Rectal Adenocarcinoma Rectal Cancer Stage Rectal Cancer Metastatic Rectal Cancer Stage III Esophagus Cancer Esophageal Cancer Esophageal Neoplasms Gastric Cancer Stage Breast Cancer Breast Neoplasm Breast Adenocarcinoma Breast Cancer Stage IV Breast Cancer Stage Breast Cancer Metastatic Breast Cancer Invasive Triple Negative Breast Neoplasms Intrahepatic Cholangiocarcinoma Intrahepatic Cholangiocarcinoma Recurrent Hilar Cholangiocarcinoma Distal Cholangiocarcinoma 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	Drug: ELU001	Phase 1/Phase 2

Detailed Description

The study has 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 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

166 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Dose Escalation Dose Expansion, Simon's 2-stageDose Escalation Dose Expansion, Simon's 2-stage

Masking:

None (Open Label)

Masking Description:

Open Label

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 13, 2021

Anticipated Primary Completion Date :

Mar 15, 2024

Anticipated Study Completion Date :

Mar 15, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ELU001 Dose Escalation: Escalating doses of ELU001 Dose Expansion: Recommended Dose for Expansion (or RP2D)	Drug: ELU001 Folic-acid functionalized C'Dot-Drug-Conjugate (FA-CDC) Other Names: FA-CDC

Arm

Intervention/Treatment

Experimental: ELU001

Dose Escalation: Escalating doses of ELU001 Dose Expansion: Recommended Dose for Expansion (or RP2D)

Drug: ELU001

Folic-acid functionalized C'Dot-Drug-Conjugate (FA-CDC)

Other Names:

FA-CDC

Outcome Measures

Primary Outcome Measures

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. [28 days]
To determine the MTD and/or RP2D of ELU001 in patients with over-expressing Folate Receptor Alpha tumors. When at least 2 out of 6 patients in a given dose-level experience a dose-limiting toxicity (DLT), the dose is considered to have exceeded the MTD. The MTD, therefore, is defined as the previous highest tested dose of ELU001 that did not cause a DLT in the first cycle of treatment. In the event of emerging data during Part 1, the Sponsor may, in consultation with a dose-level safety review group, decide to define a recommended dose for expansion (in for Part 2) (RP2D) instead of the MTD. DLTs are defined as a treatment-emergent adverse event (TEAE) or abnormal laboratory value related to ELU001 treatment that result in a failure to meet the criteria for re-treatment.
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. [First dose of study drug until responses of CR or PR, assessed up to 12 months.]
Percentage of Participants with confirmed objective response as assessed by the investigator and per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 CR is defined as the disappearance of all target or non-target lesions. PR is defined as at least 30 percent (%) decrease in the sum of the longest diameters (SoD) of target lesions, taking as reference the baseline SoD.

Secondary Outcome Measures

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. [First dose of study drug until responses of CR or PR, assessed up to 12 months.]
Percentage of Participants with confirmed objective response as assessed by the investigator and per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 CR is defined as the disappearance of all target or non-target lesions. PR is defined as at least 30 percent (%) decrease in the sum of the longest diameters (SoD) of target lesions, taking as reference the baseline SoD.
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. [Date of first response (CR or PR) until the date of disease progression or up to 12 months, whichever occurs first.]
Time Measurement: DOR will begin at the date that a response has been identified (stable disease, partial response, or complete response) until the date of progressive disease (PD). PD is defined of at least a 20% increase in the sum of the longest diameters of the target lesions from data of initial response.
Part 1 and Part 2: Number of participants with adverse events as assessed by CTCAE v5.0 Safety Evaluations. [First dose of study drug up to 28 days after the last dose of study drug or up to 12 months, whichever occurs first.]
The number of participants Frequency/severity of abnormalities in vital signs measurements, physical examination findings, changes in clinical laboratory parameters, and incidence of adverse events after taking ELU001.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

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

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
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
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:

Active or ongoing 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").

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic - Phoenix, AZ	Phoenix	Arizona	United States	85054
2	Mayo Clinic - Jacksonville, FL	Jacksonville	Florida	United States	32224
3	Sarah Cannon Research Institute at Florida Cancer Specialists	Orlando	Florida	United States	32827
4	Mayo Clinic - Rochester, MN	Rochester	Minnesota	United States	55905
5	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
6	Duke University Medical Center - Duke Cancer Institute	Durham	North Carolina	United States	27719
7	Sarah Cannon Research Institute at Tennessee Oncology	Nashville	Tennessee	United States	37203
8	Mary Crowley Cancer Research	Dallas	Texas	United States	75230
9	New Experimental Therapeutics of San Antonio (NEXT Oncology)	San Antonio	Texas	United States	78229