Ensayos clínicos

Inclusion Criteria:

• Subject (or legal guardian where applicable) is willing and able to provide signed informed consent (or assent when applicable) and can follow protocol requirements.
• Have histologically- or cytologically-confirmed disease, which is relapsed/ refractory, and unresectable or metastatic disease, following at least 1 prior line of standard-of-care systemic therapy (systemic therapy may be administered with or without the use of surgery or radiation) and must not be candidates for therapies available that are known to confer clinical benefit:
  • Synovial sarcoma;
  • A SMARCB1-null tumor as determined by immunohistochemistry, fluorescent in situ hybridization, or other equivalent tests like gene mutation analysis.
• ≥ 18 years of age or ≥ 16 years old and weighs ≥ 50 kg:
  • Adolescent enrichment cohort: 16 to 17 years of age and weighs ≥ 40 kg.
• Subject able to safely swallow tablet or pill.
• Measurable disease as defined by RECIST v1.1, a lesion which is ≥ 10 mm in the longest diameter by computed tomography scan or ≥ 10 mm measurable by calipers on physical examination.
• Eastern Cooperative Oncology Group performance status ≤ 2:
  • Adolescent enrichment cohort: Lansky performance scale (LK scale): ≥ 60.
• Adequate organ function, defined as:
  • Bone marrow function: absolute neutrophil count ≥ 1.0 x 10^9 /L independent of growth factor support for ≤ 7 days prior to first dose of study drug for granulocyte colony-stimulating factor and ≤ 14 days prior to first dose of study drug for pegfilgrastim; hemoglobin ≥ 8 g/dL independent of transfusion support for ≤ 7 days prior to first dose of study drug; platelet count ≥ 75 x 10^9 /L independent of transfusion support for ≤ 3 days prior to first dose of study drug;
  • Coagulation: Prothrombin time (PT)/international normalized ratio (INR) < 1.5 x the upper limit of normal (ULN) and activated partial thromboplastin time (aPTT) < 1.5 x ULN (unless the subject is receiving anticoagulant therapy and INR and partial PT/aPTT are within therapeutic range of intended use of anticoagulants);
  • Liver function: total bilirubin ≤ 1.5 x ULN (≤ 3.0 x ULN for subjects with Gilbert’s syndrome), aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x ULN; except for subjects who have tumor infiltration of the liver, where ALT and AST ≤ 5 x ULN;
  • Renal function: must have a creatinine clearance ≥ 60 mL/min (CockcroftGault equation);
  • Cardiac function: baseline corrected QT interval using Fredericia’s formula ≤ 470 ms (adolescents 12-17 years of age: ≤ 450 ms) and a left ventricular ejection fraction ≥ 50% evaluated via echocardiogram.
• Have available archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor not previously irradiated.
• A female subject may be eligible to participate if she is not pregnant or planning a pregnancy, not breastfeeding, and at least 1 of the following conditions applies:
  • A woman of non-childbearing potential (i.e., physiologically incapable of becoming pregnant) defined as premenopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone > 40 MIU/mL and estradiol < 40 pg/mL [< 147 pmol/L] must be obtained);
  • Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use 1 of the contraception methods specified if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status prior to study enrollment.;
  • For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw, with the exact interval dependent on the type and dosage of HRT. Following confirmation of their postmenopausal status, the subject can resume use of HRT during the study without use of a contraceptive method;
  • A woman of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during study treatment and for 30 days for females after the last dose of study treatment, must:
    • Have 2 negative pregnancy tests verified by the investigator prior to the first dose of CFT8634;
    • Have serum pregnancy test within 14 days prior to Cycle 1 Day 1;
    • Urine pregnancy test within 24 hours prior to first dose;
    • Agree to having ongoing pregnancy tests during the study and after discontinuation of the study.
  • Highly effective contraception methods include:
    • Female sterilization, total hysterectomy, or tubal ligation at least 6 weeks before taking study treatment;
    • For male partners of female subjects: Male sterilization (at least 6 months prior to screening);
    • Use of 2 reliable forms of contraception without interruption at least 30 days prior to first dose, during the conduct of the study including periods of dose interruptions of the study treatment, and for 30 days for females after discontinuation of CFT8634.
• A male subject must have either had a prior vasectomy or agree to use a condom during the treatment period and for at least 90 days after the last dose of study treatment.
• Males must refrain from donating sperm while taking CFT8634 and for 90 days after discontinuation.
• Females must refrain from donating ova while taking CFT8634 and for 30 days after discontinuation.
• Subjects must refrain from donating blood during study treatment and for 30 days after discontinuation.

Exclusion Criteria:

• Has received major surgery within 3 weeks prior to the planned first dose of CFT8634:
  • Minor surgery (e.g., minor biopsy of extracranial site, central venous catheter placement, shunt revision) is permitted within 3 weeks prior to enrollment.
• Has received standard of care or investigational systemic anti-neoplastic therapy within 14 days or 5 half-lives, whichever is shorter, prior to the planned first dose of CFT8634.
• Has received radiation therapy within 14 days prior to the planned first dose of CFT8634.
• Prior treatment with a BRD9 degrader, unless approved following discussion with the Sponsor.
• Subjects with central nervous system (CNS) involvement (primary tumor or metastatic disease), except in the following circumstances:
  • Subjects with previously treated brain metastases may be permitted to participate provided they are stable (without evidence of progression by imaging 4 weeks prior to the first dose of study treatment and any neurologic symptoms have stabilized), have no evidence of new or enlarging brain metastases, and, if they are taking corticosteroids, they are on stable or tapering doses for at least 7 days prior to first dose of study treatment. Antiseizure therapy is permitted provided the medication is not otherwise excluded and seizures have been controlled for at least 4 weeks since the last antiseizure medication adjustment;
  • Subjects with asymptomatic brain metastases found on screening magnetic resonance imaging (MRI) may be permitted to be entered into the study without prior radiation therapy to the brain if they do not require immediate surgical or radiation therapy in the opinion of the treating investigator and in the opinion of a radiation therapy or neurosurgical consultant.
• Subject has any evidence of a CNS bleed including intratumoral hemorrhage.
• Known bleeding diathesis.
• Impaired cardiac function or clinically significant cardiac disease including any of the following:
  • Congestive heart failure requiring treatment, with at least a New York Heart Association Class II;
  • Uncontrolled arterial hypertension;
  • Clinically significant arrythmias (subjects well-controlled on medication may be considered eligible following discussion and documented approval of the Sponsor) d. Unstable angina, myocardial infarction, or stroke within 6 months prior to the planned first dose of study treatment.
• Presence of inflammatory vascular disease or microangiopathy (e.g., thrombotic microangiopathies, hemolytic uremic syndrome [HUS], atypical HUS).
• Known malignancy, other than study indication, that is progressing or has required treatment within the past 3 years.
  • Subjects with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Received live, attenuated vaccine within 4 weeks of first dose of study treatment.
• Known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
• Subjects with a history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or at risk for HBV/HCV infection must have a negative HBV/HCV test to be considered eligible for this study.
• Had a venous thrombosis within 2 weeks prior to first dose of study drug.
  • Note: Subjects with a history of a deep vein thrombosis > 2 weeks prior to the first dose of study drug who are stable on anticoagulation therapy may be eligible for this study.
• Uncontrolled active systemic infection or any life-threatening illness, medical condition, or organ system dysfunction that could compromise the subject’s safety or put the study outcomes at undue risk.
• Subjects with gastrointestinal absorption issues (e.g., malabsorption syndrome or other illness that could affect oral absorption).
• Concurrent administration of strong cytochrome P450 (CYP) 3A4 inhibitors and inducers, and multidrug resistance mutation 1 inhibitors.
  • Note: If a subject can be switched to a similar agent that is not a strong CYP3A modulator or is a weak CYP3A modulator they may be permitted to enroll in the study.
• Proton pump inhibitor (PPI) drugs must be discontinued at least 7 days prior to the first dose of study drug and H2 blockers should be discontinued at least 24 hours prior to the start of study drug. Other antacid medication, like calcium containing medications, may be administered at least 6 hours from study treatment.
• Presence of grade > 2 toxicity (Common Terminology Criteria for Adverse Events v5.0) due to prior cancer therapy (subjects with alopecia may be enrolled).
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound results of the study, interfere with the subject’s participation for full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has a known psychiatric or substance abuse disorder that would interfere with cooperating with requirements of the study.
• Is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 30 days (female) or 90 days (male) after the last dose of study treatment/discontinuation.
• Previously identified hypersensitivity to components of the study treatment or excipients.

Eligibility last updated 6//28/22. Questions regarding updates should be directed to the study team contact.