| Eligibility |
Inclusion Criteria:
1. Subject (and legal guardian where applicable) is (are) willing and able to provide
signed informed consent (or assent, where applicable) and can follow protocol
requirements
2. Subject has histologically or cytologically confirmed synovial sarcoma or SMARCB1-null
sold tumor that is relapsed/refractory, and unresectable or metastatic; the subject
must not be a candidate for available therapies that are known to confer clinical
benefit
a. Phase 1: subject must have received =1 prior line of systemic anticancer therapy
considered to be Standard of Care per the Investigator's judgment, in the metastatic
or unresectable setting b. Phase 2: i. Arm A: subject must have received only 1-2
prior lines of systemic anticancer therapy considered to be Standard of Care per the
Investigator's judgment, in the metastatic or unresectable setting ii. Arm B: subject
must have received =1 prior line of systemic anticancer therapy considered to be
Standard of Care per the Investigator's judgment, in the metastatic or unresectable
setting
3. Subject must be:
- =18 years of age (no minimum weight),
- =16 and <18 years old and weighs =50 kg,
- =12 and <16 years of age and weighs =40kg,
- or =16 and <18 years of age and weighs =40kg and <50kg
4. Subject must be able to safely swallow capsules
5. Subject must have measurable disease as defined by RECIST v1.1
6. Subject must have Eastern Cooperative Oncology Group performance status =2 or Lansky
performance scale (LK scale) = 60
7. Subject must have adequate organ function, defined as:
1. Bone marrow function: absolute neutrophil count =1.0 x 109/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 peg-filgrastim; hemoglobin =8 g/dL independent of transfusion support
for =7 days prior to first dose of study drug; platelet count =75 x 109 /L
independent of transfusion support for =3 days prior to first dose of study drug
2. Coagulation: Prothrombin time (PT)/international normalized ratio (INR) <1.5x the
upper limit of normal (ULN) and activated partial thromboplastin time (aPTT)
<1.5x ULN (unless the subject is receiving anticoagulant therapy and INR and
partial PT/aPTT are within therapeutic range of intended use of anticoagulants)
3. Liver function: total bilirubin =1.5x ULN (=3.0x ULN for subjects with Gilbert's
syndrome), aminotransferase (ALT) and aspartate aminotransferase (AST) =3.0x ULN;
except for subjects who have tumor infiltration of the liver, where ALT and AST
=5x ULN
4. Renal function: must have a creatinine clearance =60 mL/min (via Cockcroft-Gault
equation, institutional standard, or measured)
5. 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 or multi-gated acquisition (MUGA) scan
8. Availability of archival tumor tissue sample or newly obtained core/excisional biopsy
of a tumor not previously irradiated
9. A female subject may be eligible to participate if she is not pregnant or planning a
pregnancy, not breastfeeding, and following protocol mediated guidance to avoid
pregnancy
10. A male subject must have had a prior vasectomy and agree to use a condom during the
treatment period and for at least 90 days after the last dose of study treatment
11. A male subject must refrain from donating sperm while taking CFT8634 and for 90 days
post-last dose
12. A female subject must refrain from donating ova while taking CFT8634 and for 180 days
after discontinuation
13. All subjects must refrain from donating blood and blood products while receiving study
drug and for 30 days post-last dose
Exclusion Criteria:
1. Subject has had major surgery within 21 days prior to the planned first dose of
CFT8634
a. Minor surgery (eg, minor biopsy of extracranial site, central venous catheter
placement, shunt revision) is permitted within 21 days prior to first dose of CFT8634
2. Subject 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
3. Subject has received radiation therapy within 14 days prior to the planned first dose
of CFT8634
4. Prior treatment with BRD9 degrader
5. Subject has central nervous system (CNS) involvement (primary tumor or metastatic
disease), except in the following circumstances:
1. Subjects with previously treated brain metastases may be permitted to participate
provided they are stable (without evidence of progression by imaging 14 days
prior to the first dose of study drug 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 drug. Antiseizure therapy is permitted provided
the medication is not otherwise excluded and seizures have been controlled for at
least 28 days since the last antiseizure medication adjustment
2. 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
6. Subject has any evidence of a CNS bleed including intra-tumoral hemorrhage
7. Subject has known bleeding diathesis
8. Subject has impaired cardiac function or clinically significant cardiac disease (i.e.
uncontrolled heart disease/hypertension, clinically significant arrythmias, unstable
angina/myocardia infarction/stroke within 180 days prior to screening)
9. Subject with presence of inflammatory vascular disease or microangiopathy (eg,
thrombotic microangiopathies, hemolytic uremic syndrome [HUS], atypical HUS)
10. Subject with known malignancy, other than study indication, that is progressing or has
required treatment within the past 3 years
a. Subject with basal cell carcinoma of the skin, squamous cell carcinoma of the skin,
or carcinoma in situ (i.e. breast carcinoma, cervical cancer in situ) that have
undergone potentially curative therapy are not excluded
11. Subject has received live, attenuated vaccine within 28 days prior to first dose
administration
12. Subject with known history of human immunodeficiency virus (HIV) infection
13. Subject had a venous thrombosis within 14 days prior to first dose of study drug
14. Subject with gastrointestinal absorption issues (e.g., malabsorption syndrome or other
illness that could affect oral absorption).
15. Concurrent administration of strong cytochrome P450 (CYP) 3A4 inhibitors and inducers,
and multidrug resistance mutation 1 (MDR1) inhibitors.
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