IRB Study Number 24-1159
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objectives:
Phase 1
• To characterize the safety and tolerability of REC-1245
• To identify the maximum tolerated dose (MTD) and / or recommended phase 2 dose (RP2D) of REC-1245
Phase 2
• To characterize the safety and tolerability of REC-1245
• To evaluate the preliminary anti-tumor activity of REC-1245 as measured by Objective Response Rate (ORR)
Secondary Objectives:
Phase 1
• To characterize the pharmacokinetic (PK) profile of REC-1245
• To evaluate the preliminary anti-tumor activity of REC-1245 as measured by ORR
Phase 2
• To assess the anti-tumor activity of REC-1245 as measured by other efficacy endpoints
Inclusion Criteria
Age ≥ 18 years old
Have signed informed consent and are willing and able to comply with study procedures and scheduled visits
Have histologically-confirmed unresectable, locally advanced, or metastatic select solid tumors or select relapsed / refractory lymphoma (see Appendix C)
Have experienced progressive disease, relapsed disease, or be intolerant to at least one established standard systemic anti-cancer treatment for a given tumor type, or 2 prior lines of systemic therapy for relapsed or refractory lymphoma or in the opinion of the Investigator have been considered ineligible for standard therapy.
Note: Indolent B-cell and T-cell lymphoma patients in need of immediate cytoreductive therapy are not eligible unless the patient has no remaining treatment choice with potential benefit, because the efficacy of the study drug is not established.
ECOG performance status ≤ 1
Measurable disease at baseline per RECIST 1.1 / Lugano criteria and documented by computed CT and / or MRI. PET-CT may be utilized for Lymphoma/Lugano criteria, if utilized for solid tumors a CT scan of diagnostic quality for RECIST measurements is required
Note: Lesions treated previously with radiation must demonstrate clear evidence of radiographic progression since the completion of prior radiotherapy and prior to study enrollment
All toxicities from prior anti-cancer therapies have resolved to ≤ Grade 1 or the participant’s previous baseline
Acceptable laboratory parameters:
• Albumin ≥ 2.8 g/dL
• Platelet count ≥ 100,000/L
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count ≥ 1,500/μL
• ALT / AST ≤ 3.0 times ULN
− ALT / AST ≤ 5 × ULN for participants with liver metastases
• Total bilirubin ≤ 1.5 ULN or ≤ 3 x ULN for participants with Gilbert’s disease
− Direct bilirubin ≤ 1.5 ULN for participants with total bilirubin > 1.5 ULN
• Creatinine clearance ≥ 60 mL/minute based on the Cockcroft-Gault equation
- Females must not be pregnant or nursing and be either:
a. Of non-childbearing potential [defined as having undergone surgical sterilization (hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or being postmenopausal (i.e. greater than 45 years old with amenorrhea for ≥ 12 months AND a serum follicle stimulating hormone level > 40 mIU/mL)
b. Of childbearing potential, not surgically sterilized, and between menarche and one year post menopause must:
• Have a negative serum or urine pregnancy test performed within 72 hours prior to the initiation of study drug administration
• Be willing to use a highly effective contraception throughout the study from screening through 30 days after the last dose of study drug (Appendix A)
• Agree to practice true abstinence, if this is the established and preferred contraception method for the participant and is defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments (time of consent through 30days after the last dose of study drug). Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea method are not acceptable methods of contraception. Female and male condoms should not be used together.
- Male participants with partners of childbearing potential, even if surgically sterilized (i.e., status post-vasectomy or bilateral orchidectomy) must agree to:
• Use effective barrier contraception from the time of screening through 90 days after the last dose of study drug (Appendix A)
or
• Agree to practice true abstinence, if this is the established and preferred contraception method by the participant and is defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments (time of consent through 90days after the last dose of study drug). Periodic abstinence [e.g., calendar, symptothermal, post-ovulation methods], withdrawal, spermicides only, and lactational amenorrhea method are not acceptable methods of contraception. Female and male condoms should not be used together.
• In addition, it is recommended that male participants should encourage their partners to use contraception for the same period of time
Additionally, male participants acknowledge and agree to participation knowing that there is a chance of sterility (no longer being able to have children) following treatment with the study drug
- Must be willing and able to comply with clinic visits and procedures outlined in the study protocol
Exclusion Criteria
Received treatment with another RBM39 degrader
Participants with symptomatic or unstable central nervous system (CNS) primary tumor or metastases and / or carcinomatous meningitis. Participants with documented treated CNS metastases stable for at least two weeks may be enrolled at the discretion of the Investigator.
Major surgery within six weeks from treatment initiation
Clinically significant gastrointestinal disorders or GI malabsorption including:
• Gastrointestinal perforation or unhealed ulcerations < 6 months prior to study drug administration. Participants must have documented evidence (e.g., upper endoscopy, colonoscopy) of completely healed area of prior perforation
• Clinically significant gastrointestinal bleeding < 3 months prior to study drug administration
• Pancreatitis < 6 months prior to study drug administration
• History of Crohn’s disease or ulcerative colitis, a participant with controlled disease may be enrolled with Sponsor approval
Known hypersensitivity to any component of REC-1245
Second primary invasive malignancy not in remission for ≥ 1 year. Exceptions include nonmelanoma skin cancer, cervical carcinoma in situ, resected melanoma in situ, or any malignancy considered to be indolent and never required therapy.
QTcF prolongation >470 msec at screening or history of long QTc syndrome
Clinically significant cardiovascular vascular disease ≤ 6 months before first dose
• Myocardial infarction or unstable angina
• Clinically significant cardiac arrhythmias
• Uncontrolled hypertension: systolic blood pressure (SBP) > 180 mmHg, diastolic blood pressure (DBP) > 100 mmHg
• Pulmonary embolism, symptomatic cerebrovascular events or any other serious cardiac condition (e.g., pericardial effusion or restrictive cardiomyopathy)
• Congestive heart failure (New York Heart Association class III-IV)
• Myocarditis / clinically significant pericarditis
Venous or arterial thrombosis within the past 6 months
Any serious underlying medical or psychiatric condition that would preclude understanding and rendering of informed consent or impair the ability of the participant to receive or tolerate the planned treatment
Recent or ongoing serious infection including the following:
• Any uncontrolled Grade 3 or higher (per Common Terminology Criteria for Adverse Events [CTCAE v 5.0]) viral, bacterial, or fungal infection within two weeks prior to the first dose of REC-1245. Routine antimicrobial prophylaxis using agents that are not considered strong CYP3A4 inhibitors (i.e., most imidazole fungicides) is allowed.
• Uncontrolled infection with human immunodeficiency virus (HIV). Participants on stable highly active antiretroviral therapy with undetectable viral load and normal CD4 counts for at least six months prior to study entry are eligible. Serological testing for HIV at screening is not required.
• Known to be positive for hepatitis B virus (HBV) surface antigen, or any other positive test for hepatitis B indicating acute or chronic infection. Participants who are or have received anti-HBV therapy and have undetectable HBV DNA for at least six months prior to study entry are eligible. Serological testing for HBV at screening is not required.
• Known active hepatitis C virus (HCV) as determined by positive serology and confirmed by polymerase chain reaction (PCR). Participants on or having received antiviral therapy are eligible provided they are virus-free by PCR for at least six months prior to study entry. Serological testing for HCV at screening is not required.
• Known active or latent tuberculosis (testing at screening not required)
Use of proteosome, OAT3, and / or neddylation inhibitors are prohibited for at least 14 days prior to Study Day 1 and throughout the treatment period
Use of moderate / strong CYP2C9 inducers, CYP1A2 substrates, CYP2B6 substrates, and strong/moderate CYP2C9 inhibitors are prohibited for at least 14 days prior to Study Day 1 and throughout the treatment period
Recent prior systemic anti-cancer treatment:
• For cytotoxic chemotherapy, small molecule inhibitors, radiation, or similar investigational treatments within the last two weeks or within five half-lives (if known) from REC-1245 administration, whichever is shorter
• For monoclonal antibodies or similar experimental therapies: within the last three weeks or five half-lives (if known) from REC-1245 administration, whichever is shorter
• Antibody drug conjugates and radioimmunoconjugates or other similar experimental therapies within the last six weeks or five half-lives from REC-1245 administration, whichever is shorter
- Is currently participating in a study of an investigational therapy or device or has participated and received an investigation therapy or device within 4 weeks of REC-1245 administration
