A Phase 1 dose escalation study to determine if SNDX-6352 as monotherapy and SNDX-6352 in
combination with a fixed dose of durvalumab will be sufficiently safe and well-tolerated at
biologically active doses to warrant further investigation in patients with solid tumors.
Inclusion Criteria for Phase 1a and Phase 1b
Patients meeting all of the following criteria are considered eligible to participate in
1. Signed written informed consent form (ICF).
2. Male or female patients aged ≥18 years.
3. Patients with histopathologically confirmed unresectable, recurrent, locally-advanced,
or metastatic solid tumors, with evaluable disease and must have progressed following
prior treatment and have no standard therapy alternatives left (ie: patients must not
be candidates for regimens known to provide clinical benefit).
4. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at the study
5. Has adequate organ and bone marrow function within 21 days before enrollment as
a. Hematological laboratory values: i. Absolute Neutrophil Count (ANC) ≥1.5 × 109/L
ii. Platelets ≥100 × 109/L iii. Hemoglobin ≥9 g/dL b. Renal laboratory values: i.
Creatinine ≤1.5 times the Upper Limit of Normal (ULN) OR ii. Measured or calculated
(per institutional standard) creatinine clearance (CrCl) ≥60 mL/min according to the
Cockcroft-Gault formula or measured 24-hour creatinine clearance (or local
institutional standard measure) for patient with creatinine level > 1.5 times
iii. Glomerular filtration rate may be used instead of creatinine or CrCl. c. Hepatic
laboratory values: i. Total bilirubin ≤1.5 times ULN or ii. Direct bilirubin ≤ULN for
patients with total bilirubin >1.5 times ULN iii. AST and ALT ≤2.5 times ULN d.
Creatine kinase ≤ ULN
6. Experienced resolution of toxic effect(s) of the most recent prior anti-cancer therapy
to Grade ≤1 (except alopecia) per NCI CTCAE v5.0 If a patient underwent major surgery
or radiation therapy of >30 Gray, the patient must have recovered from the toxicity
and/or complications from the intervention.
Note: Patients with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia are an exception to
this criterion and may qualify for the study.
7. Evidence of post-menopausal status or negative urinary or serum pregnancy test for
female pre-menopausal patients. Women will be considered post-menopausal if they have
been amenorrheic for 12 months without an alternative medical cause. The following
age-specific requirements apply:
- Women <50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous hormonal
treatments and if they have luteinizing hormone and follicle-stimulating hormone
levels in the post-menopausal range for the institution or underwent surgical
sterilization (bilateral oophorectomy or hysterectomy).
- Women ≥50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of all exogenous hormonal
treatments, had radiation-induced menopause with last menses >1 year ago, had
chemotherapy-induced menopause with last menses >1 year ago, or underwent
surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or
8. Female patients of childbearing potential who are not abstinent and intend to be
sexually active with a nonsterilized male partner must use at least 1 highly effective
method of contraception (Table 11) from the time of screening throughout the total
duration of the study drug treatment and 90 days after the last dose of study drug.
Non-sterilized male partners of a female patient of childbearing potential must use
male condom plus spermicide throughout this period. Cessation of birth control after
this point should be discussed with a responsible physician. Periodic abstinence, the
rhythm method, and the withdrawal method are not acceptable methods of birth control.
Female patients should also refrain from breastfeeding throughout this period.
9. Non-sterilized male patients who are not abstinent and intend to be sexually active
with a female partner of childbearing potential must use a male condom plus spermicide
from the time of screening throughout the total duration of the study drug treatment
and 90 days after the last dose of study drug. However, periodic abstinence, the
rhythm method, and the withdrawal method are not acceptable methods of contraception.
Male patients should refrain from sperm donation throughout this period.
10. Must have a life expectancy of at least 12 weeks.
Additional Inclusion Criteria for Phase 1b 11. Body weight > 30 kg 12. No prior exposure to
immune-mediated therapy including, but not limited to, other anti CTLA-4, anti-PD-1,
anti-PD-L1, and anti-PD-L2 antibodies, excluding therapeutic anticancer vaccines.
Exclusion Criteria for Phase 1a and Phase 1b
Patients meeting any of the following criteria are not eligible for study participation:
1. Diagnosis of immunodeficiency or receiving systemic corticosteroid therapy or any
other form of immunosuppressive therapy within 14 days prior to the first dose of
a. Exceptions: 1) The use of physiologic doses of corticosteroids (i.e., ≤10 mg per
day of equivalent prednisone) is allowed; 2) Steroids with no or minimal systemic
effect (topical, inhalation) are allowed; 3) Replacement therapy (e.g., thyroxine,
insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency) is not considered a form of systemic treatment; (4) Steroids as
premedication for hypersensitivity reactions (e.g., CT scan premedication).
2. Previously treated with a CSF-1, CSF-1R, and/or IL-34-blocking agents
3. Psychiatric illness/social situations that would limit compliance with study
requirement, substantially increase risk of incurring AEs or compromise the ability of
the patient to give written informed consent
4. History or current evidence of any condition, therapy, or laboratory abnormality that
might confound the results of the study, interfere with the patient's participation
for the full duration of the study, or is not in the patient's best interest to
participate, in the opinion of the treating Investigator, including, but not limited
1. Active or prior documented autoimmune or inflammatory disorders (see Appendix 3
for complete list).
2. History of active primary immunodeficiency
3. Known active or latent tuberculosis (clinical evaluation that includes clinical
history, physical examination and radiographic findings, and tuberculosis testing
in line with local practice).
4. Myocardial infarction or arterial thromboembolic events within 6 months prior to
enrollment or severe or unstable angina, New York Heart Association (NYHA) (see
Appendix 2) Class III or IV disease, or a QTc interval > 470 msec. History of QTc
prolongation, ventricular fibrillation, ventricular tachycardia or Torsades de
5. Symptomatic congestive heart failure, cardiac arrhythmia, uncontrolled
hypertension or diabetes mellitus.
6. Active infection requiring systemic therapy.
7. Interstitial lung disease
8. Serious chronic gastrointestinal conditions associated with diarrhea
9. Has untreated central nervous system (CNS) metastases and/or carcinomatous
meningitis identified either on the baseline brain imaging (please see Appendix A
(RECIST)) for details on the imaging modality) obtained during the screening
period or identified prior to signing the ICF. Patients whose brain metastases
have been treated may participate provided they show radiographic stability
(defined as 2 brain images, both of which are obtained after treatment to the
brain metastases. These imaging scans should both be obtained at least four weeks
apart and show no evidence of intracranial progression). In addition, any
neurologic symptoms that developed either as a result of the brain metastases or
their treatment must have resolved or be stable either, without the use of
steroids, or are stable on a steroid dose of ≤10 mg/day of prednisone or its
equivalent for at least 14 days prior to the start of treatment. Brain metastases
will not be recorded as RECIST Target Lesions at baseline.
5. Received a live attenuated vaccine within 30 days of the first dose of study drug.
Note: Patients, if enrolled, should not receive live vaccine whilst receiving study
drug and up to 30 days after the last dose of study drug.
6. Administration of colony stimulating factors (including granulocyte-colony stimulating
factor [G-CSF], granulocyte macrophage-colony stimulating factor [GM-CSF], or
recombinant erythropoietin) within 4 weeks prior to the first dose of study drug
7. Concurrent enrolment in another clinical study, unless it is an observational
(non-interventional) clinical study or during the follow-up period of an
8. Received chemotherapy, anti-cancer mAb, targeted small molecule or other systemic
anti-cancer therapy within 4 weeks of the first dose of study drug. However, patients
receiving conventional and investigational small molecule targeted therapies that are
not expected to have delayed toxicities may enter the study 5 half-lives or 28 days
after the last dose of the compound, whichever is shorter.
9. Currently receiving treatment with any other agent listed on the prohibited medication
list (see Section 7.11).
10. Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
11. Known active hepatitis B (e.g., hepatitis B surface antigen-reactive) or hepatitis C
(e.g., hepatitis C virus ribonucleic acid [qualitative]). Patients with past hepatitis
B virus (HBV) infection or resolved HBV infection (defined as the presence of
hepatitis B core antibody [HBc Ab] and absence of HBsAg) are eligible. Patients
positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain
reaction is negative for HCV RNA.
12. Known alcohol or drug abuse.
13. Known psychiatric or substance abuse disorders that would interfere with cooperation
with the requirements of the study.
14. Legal incapacity or limited legal capacity.
15. Evidence of muscle disorders or muscle injury that are known to cause serum creatine
kinase (CK) elevation
16. Current pneumonitis or has a history of (non-infectious) pneumonitis that required
17. Known allergy or hypersensitivity to any of the study drugs or any of the study drug
18. Major surgical procedure (as defined by the Investigator) within 28 days prior to the
first dose of study drug. Note: Local surgery of isolated lesions for palliative
intent is acceptable.
19. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of
radiation within 4 weeks or palliative radiation therapy within 2 weeks of the first
dose of study drug
20. Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential who are not willing to employ effective birth control from
screening to 90 days after the last dose of study drug
Additional Exclusion Criteria for Phase 1b
21. History of allogenic organ transplantation.
22. Patients who have received prior anti-PD-1, anti PD-L1 or anti CTLA-4.