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A Phase 1 Study to Investigate SNDX-6352 Alone or in Combination With Durvalumab in Patients With Solid Tumors

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ClinicalTrials.gov Identifier: NCT03238027
Recruitment Status : Recruiting
First Posted : August 3, 2017
Last Update Posted : November 29, 2018
Sponsor:
Information provided by (Responsible Party):
Syndax Pharmaceuticals

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Solid Tumor Metastatic Tumor Locally Advanced Malignant Neoplasm Unresectable Malignant Neoplasm Drug: SNDX-6352 Drug: Durvalumab Phase 1

Detailed Description:
This is an open label, multi-center Phase 1 study consisting of Phase 1a and Phase 1b. The study will evaluate SNDX-6352 monotherapy (in Phase 1a) and SNDX-6352 combined with durvalumab (in Phase 1b) in patients with advanced solid tumors which must have progressed following prior treatment and have no standard therapy alternatives left (i.e.. patients must not be candidates for regimens known to provide clinical benefit). The primary objective will be to determine the MTD and/or RP2D of SNDX-6352 as monotherapy (Phase 1a) and in combination with durvalumab (Phase 1b) as evaluated by the incidence of AEs that are defined as DLTs. In both study phases, a standard "3+3"dose escalation schema will be used to determine an MTD with 3-6 evaluable patients enrolled per dose level. The RP2D will be determined based on data from the dose escalation patients as reviewed by the Safety Review Committee (SRC; comprised of investigators and the Sponsor).

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Initially in both phases, 3 patients will receive SNDX-6352 at 1 mg/kg IV on C1D1 and again on C1D15 of a 28-day cycle. Phase 1b only will also receive a fixed dose of 1500mg durvalumab IV on C1D1. If no DLTs are noted, 3 more patients will be treated at the next higher dose level (3 mg/kg). If 1 DLT is observed in 1 of 3 patients, 3 more patients will be treated at that starting dose level (1 mg/kg). If 2 or more DLTs are observed in 3-6 patients at the starting dose, the study will be terminated or a lower dose will be considered. If the safety profile is acceptable, escalation to SNDX-6352 doses of 3, 6 and 10mg/kg are planned for the 1a and for the 1b, doses of 3 and 6 mg/kg of SNDX-6352 in combination with a fixed dose of 1500mg of durvalumab are planned. The MTD will be considered to have been exceeded if 2 or more patients in a dose group experience a DLT; in this case, the next lower dose group which has been evaluated will be considered as the MTD.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1, Open-Label Dose Escalation Trial to Investigate Safety and Tolerability of SNDX-6352 Monotherapy and SNDX-6352 in Combination With Durvalumab in Patients With Unresectable, Recurrent, Locally-Advanced, or Metastatic Solid Tumors
Actual Study Start Date : September 1, 2017
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : February 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: Ph1a D1: 1 mg/kg SNDX-6352
Three (3) patients receive starting dose of 1 mg/kg of SNDX-6352 and are followed for possible DLTs. If one DLT is observed in 1 of 3 patients, an additional 3 patients will be enrolled at this dose level. If no DLTs are noted in any of the 3 patients, next dosing arm will commence following review by Scientific Review Committee.
Drug: SNDX-6352
Humanized IgG4 mAb that blocks colony stimulating factor 1 receptor (CSF-1R)

Experimental: Ph1a D2: 3 mg/kg SNDX-6352
Three (3) patients receive next higher dose of 3 mg/kg of SNDX-6352 and are followed for possible DLTs. If one DLT is observed in 1 of 3 patients, an additional 3 patients will be enrolled at this dose level. If no DLTs are noted in any of the 3 patients, next dosing arm will commence following review by Scientific Review Committee.
Drug: SNDX-6352
Humanized IgG4 mAb that blocks colony stimulating factor 1 receptor (CSF-1R)

Experimental: Ph1a D3: 6 mg/kg SNDX-6352
Three (3) patients receive next higher dose of 6 mg/kg of SNDX-6352 and are followed for possible DLTs. If one DLT is observed in 1 of 3 patients, an additional 3 patients will be enrolled at this dose level. If no DLTs are noted in any of the 3 patients, next dosing arm will commence following review by Scientific Review Committee.
Drug: SNDX-6352
Humanized IgG4 mAb that blocks colony stimulating factor 1 receptor (CSF-1R)

Experimental: Ph1a D4: 10 mg/kg SNDX-6352
Three (3) patients receive next higher dose of 10 mg/kg of SNDX-6352 and are followed for possible DLTs. If one DLT is observed in 1 of 3 patients, an additional 3 patients will be enrolled at this dose level. If no DLTs are noted in any of the 3 patients, next dosing arm will commence following review by Scientific Review Committee.
Drug: SNDX-6352
Humanized IgG4 mAb that blocks colony stimulating factor 1 receptor (CSF-1R)

Experimental: Ph1b D1: 1 mg/kg SNDX-6352+1500mg durva
Three (3) patients receive starting dose of 1 mg/kg of SNDX-6352 every two weeks and 1500mg durvalumab every four weeks and are followed for possible DLTs. If one DLT is observed in 1 of 3 patients, an additional 3 patients will be enrolled at this dose level. If no DLTs are noted in any of the 3 patients, next dosing arm will commence following review by Scientific Review Committee. If 1 DLT is observed in 1 of 3 patients, then 3 additional patients will be treated at the 1 mg/kg SNDX-6352 dose level; if none of the 3 additional patients experience a DLT (i.e. 1 of 6), the dose will be escalated to an intermediate dose of 2 mg/kg. Escalation from 2 mg/kg to 3 mg/kg will follow the general dose escalation rules described above for both study phases.
Drug: SNDX-6352
Humanized IgG4 mAb that blocks colony stimulating factor 1 receptor (CSF-1R)

Drug: Durvalumab
Durvalumab (MEDI4736) is a humanized IgG1 kappa mAb that blocks the interaction of PD-L1 with PD-1 CD80 (B7.1) molecules
Other Name: MEDI4736

Experimental: Ph1b D2: 3 mg/kg SNDX-6352+1500mg durva
Three (3) patients receive next higher dose of 3 mg/kg of SNDX-6352 every two weeks and 1500mg durvalumab every four weeks and are followed for possible DLTs. For cohorts with doses ≥3 mg/kg, a sentinel recruitment approach will be utilized. Initially 1 patient in each cohort will be treated with the combination therapy and safety will be evaluated by SRC at Cycle 1, Day 8; if no safety concerns are identified, the next 2 patients can be treated in that cohort. If one DLT is observed in 1 of 3 patients, an additional 3 patients will be enrolled at this dose level. If no DLTs are noted in any of the 3 patients, next dosing arm will commence following review by Scientific Review Committee.
Drug: SNDX-6352
Humanized IgG4 mAb that blocks colony stimulating factor 1 receptor (CSF-1R)

Drug: Durvalumab
Durvalumab (MEDI4736) is a humanized IgG1 kappa mAb that blocks the interaction of PD-L1 with PD-1 CD80 (B7.1) molecules
Other Name: MEDI4736

Experimental: Ph1b D3: 3 mg/kg SNDX-6352+1500mg durva
Three (3) patients receive next higher dose of 6 mg/kg of SNDX-6352 every two weeks and 1500mg durvalumab every four weeks and are followed for possible DLTs. For cohorts with doses ≥3 mg/kg, a sentinel recruitment approach will be utilized. Initially 1 patient in each cohort will be treated with the combination therapy and safety will be evaluated by SRC at Cycle 1, Day 8; if no safety concerns are identified, the next 2 patients can be treated in that cohort. If one DLT is observed in 1 of 3 patients, an additional 3 patients will be enrolled at this dose level. If no DLTs are noted in any of the 3 patients, next dosing arm will commence following review by Scientific Review Committee.
Drug: SNDX-6352
Humanized IgG4 mAb that blocks colony stimulating factor 1 receptor (CSF-1R)

Drug: Durvalumab
Durvalumab (MEDI4736) is a humanized IgG1 kappa mAb that blocks the interaction of PD-L1 with PD-1 CD80 (B7.1) molecules
Other Name: MEDI4736




Primary Outcome Measures :
  1. Phase 1a: Determination of any Dose limiting toxicities (DLT)s of SNDX-6352 [ Time Frame: Approximately 9 months (from first dose to 90-day follow-up post-last dose) ]
    All patients treated with SNDX-6352 across all treatment arms (dosing levels) will have safety assessed in order to determine any dose-limiting toxicities (DLT)s.

  2. Phase 1a: Determination of Maximum tolerable dose (MTD) of SNDX-6352 [ Time Frame: Approximately 9 months (from first dose to 90-day follow-up post-last dose) ]
    All patients treated with SNDX-6352 across all treatment arms (dosing levels) will have safety assessed in order to determine the MTD.

  3. Phase 1a: Determination of Recommended Phase 2 dose (RP2D) of SNDX-6352 [ Time Frame: Approximately 9 months (from first dose to 90-day follow-up post-last dose) ]
    All patients treated with SNDX-6352 across all treatment arms (dosing levels) will have safety assessed in order to determine the RP2D.

  4. Phase 1b: Determination of any Dose limiting toxicities (DLT)s of SNDX-6352 when given in combination with a fixed dose of durvalumab [ Time Frame: Approximately 9 months (from first dose to 90-day follow-up post-last dose) ]
    All patients treated with SNDX-6352 in combination with a fixed dose of durvalumab across all treatment arms (dosing levels) will have safety assessed in order to determine any dose-limiting toxicities (DLT)s.

  5. Phase 1b: Determination of Maximum tolerable dose (MTD) of SNDX-6352 when given in combination with a fixed dose of durvalumab [ Time Frame: Approximately 9 months (from first dose to 90-day follow-up post-last dose) ]
    All patients treated with SNDX-6352 in combination with a fixed dose of durvalumab across all treatment arms (dosing levels) will have safety assessed in order to determine the MTD.

  6. Phase 1b: Determination of Recommended Phase 2 dose (RP2D) of SNDX-6352 when given in combination with a fixed dose of durvalumab [ Time Frame: Approximately 9 months (from first dose to 90-day follow-up post-last dose) ]
    All patients treated with SNDX-6352 in combination with a fixed dose of durvalumab across all treatment arms (dosing levels) will have safety assessed in order to determine the RP2D.


Secondary Outcome Measures :
  1. Phase 1a: PK endpoint of Cmax (maximum observed concentration) for SNDX-6352 as dose levels increase across different treatment groups. [ Time Frame: Approximately 6 months (from first dose to End of Treatment visit) ]
    Cmax for SDNX-6352 for SNDX-6352 will be computed.

  2. Phase 1a: PK endpoint of AUC (area under the curve) for SNDX-6352 as dose levels increase across different treatment groups. [ Time Frame: Approximately 6 months (from first dose to End of Treatment visit) ]
    AUC for SDNX-6352 for SNDX-6352 will be computed.

  3. Phase 1a: PK endpoint of Tmax (time to reach maximum observed concentration) for SNDX-6352 as dose levels increase across different treatment groups. [ Time Frame: Approximately 6 months (from first dose to End of Treatment visit) ]
    Tmax for SDNX-6352 for SNDX-6352 will be computed.

  4. Phase 1a: PK endpoint of T1/2 (apparent terminal elimination half life)) for SNDX-6352 as dose levels increase across different treatment groups. [ Time Frame: Approximately 6 months (from first dose to End of Treatment visit) ]
    T1/2 for SDNX-6352 for SNDX-6352 will be computed.

  5. Phase 1a: Evaluation of preliminary anti-tumor activity of SNDX-6352 on solid tumors [ Time Frame: Approximately 9 months (from baseline scan to 90-day follow-up post-last dose) ]
    To determine if the size and number of target lesions changes in response to treatment with SNDX-6352 by analyzing CT-Scans/MRIs per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) and irRECIST.

  6. Phase 1a: Effect of SNDX-6352 on CSF-1 and IL-34 [ Time Frame: Approximately 6 months (from first dose to End of Treatment visit) ]
    To assess change from Baseline in plasma CSF-1 and IL-34 following IV administration

  7. Phase 1a: Evaluate the immunogenicity of SNDX-6352 [ Time Frame: Approximately 6 months (from first dose to End of Treatment visit) ]
    To assess the immunogenicity of SNDX-6352 as measured by presence of anti-drug antibodies (ADA)

  8. Phase 1b: PK endpoint of Cmax (maximum observed concentration) for SNDX-6352 when given in combination with a fixed dose of durvalumab as dose levels increase across different treatment groups. [ Time Frame: Approximately 6 months (from first dose to End of Treatment visit) ]
    Cmax for SNDX-6352 will be computed.

  9. Phase 1b: PK endpoint of AUC (area under the curve) for SNDX-6352 when given in combination with a fixed dose of durvalumab as dose levels increase across different treatment groups. [ Time Frame: Approximately 6 months (from first dose to End of Treatment visit) ]
    AUC for SNDX-6352 will be computed.

  10. Phase 1b: PK endpoint of Tmax (time to reach maximum observed concentration) for SNDX-6352 when given in combination with a fixed dose of durvalumab as dose levels increase across different treatment groups. [ Time Frame: Approximately 6 months (from first dose to End of Treatment visit) ]
    Tmax for SNDX-6352 will be computed.

  11. Phase 1b: PK endpoint of T1/2 (apparent terminal elimination half-life)) for SNDX-6352 when given in combination with a fixed dose of durvalumab as dose levels increase across different treatment groups. [ Time Frame: Approximately 6 months (from first dose to End of Treatment visit) ]
    T1/2 for SNDX-6352 will be computed.

  12. Phase 1b: PK endpoint of Cmax (maximum observed concentration) for durvalumab when given in combination with SNDX-6352 as dose levels increase across different treatment groups. [ Time Frame: Approximately 6 months (from first dose to End of Treatment visit) ]
    Cmax for durvalumab will be computed.

  13. Phase 1b: PK endpoint of AUC (area under the curve) for durvalumab when given in combination with SNDX-6352 as dose levels increase across different treatment groups. [ Time Frame: Approximately 6 months (from first dose to End of Treatment visit) ]
    AUC for durvalumab will be computed.

  14. Phase 1b: PK endpoint of Tmax (time to reach maximum observed concentration) for durvalumab when given in combination with SNDX-6352 as dose levels increase across different treatment groups. [ Time Frame: Approximately 6 months (from first dose to End of Treatment visit) ]
    Tmax for durvalumab will be computed.

  15. Phase 1b: PK endpoint of T1/2 (apparent terminal elimination half-life) for durvalumab when given in combination with SNDX-6352 as dose levels increase across different treatment groups. [ Time Frame: Approximately 6 months (from first dose to End of Treatment visit) ]
    T1/2 for durvalumab will be computed.

  16. Phase 1b: Evaluation of preliminary anti-tumor activity of SNDX-6352 when given in combination with a fixed dose of durvalumab on solid tumors. [ Time Frame: Approximately 9 months (from baseline scan to 90-day follow-up post-last dose) ]
    To determine if the size and number of target lesions changes in response to treatment with SNDX-6352 by analyzing CT-Scans/MRIs per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) and irRECIST.

  17. Phase 1b: Effect of SNDX-6352 on CSF-1 and IL-34 [ Time Frame: Approximately 6 months (from first dose to End of Treatment visit) ]
    To assess change from Baseline in plasma CSF-1 and IL-34 following IV administration

  18. Phase 1b: Evaluation of the immunogenicity of SNDX-6352 [ Time Frame: Approximately 6 months (from first dose to End of Treatment visit) ]
    To assess the immunogenicity of SNDX-6352 as measured by presence of anti-drug antibodies (ADA)

  19. Phase 1b: Evaluation of the immunogenicity of durvalumab [ Time Frame: Approximately 6 months (from first dose to End of Treatment visit) ]
    To assess the immunogenicity of durvalumab as measured by presence of anti-drug antibodies (ADA)


Other Outcome Measures:
  1. Phase 1a: Effect of SNDX-6352 on CSF-1 receptor occupancy [ Time Frame: Approximately 6 months (from first dose to End of Treatment visit) ]
    To evaluate the change from Baseline in CSF-1 receptor occupancy (RO)

  2. Phase 1a: Exploration of relationship between candidate biomarker results and anti-tumor activity of SNDX-6352 [ Time Frame: Approximately 6 months (from first dose to End of Treatment visit) ]
    To investigate the relationship between candidate biomarkers (e.g., CSF-1, IL-34) and anti-tumor activity of SNDX-6352

  3. Phase 1a: Exploration of relationship between additional biomarkers and anti-tumor activity of SNDX-6352 [ Time Frame: Approximately 6 months (from first dose to End of Treatment visit) ]
    To investigate the relationship between other biomarkers (e.g., tumor infiltrating lymphocytes, PD-L1, PD-1, PD-L2, circulating classical and non-classical CD-16 monocytes in blood) and anti-tumor activity of SNDX-6352

  4. Phase 1a: Characterization of relationship in change from baseline in CSF-1, IL-34, etc. with SNDX-6352 administered intravenously. [ Time Frame: Approximately 6 months (from first dose to End of Treatment visit) ]
    To characterize the relationship in change from baseline in plasma colony stimulating factor-1 [CSF-1] interleukin-34 [IL-34]), and IFN-gamma, IL-1beta, IL-2, IL-4, IL-5, IL-6, CXCL8/IL-8, IL-10, IL-12 (p70), IL-13, TNF-alpha, CD204/206 and sCD163 with systemic PK of SNDX-6352 administered intravenously.

  5. Phase 1b: Characterization of the PD profile of SNDX-6352 and durvalumab when given in combination. [ Time Frame: Approximately 6 months (from first dose to End of Treatment visit) ]
    To characterize the pharmacodynamic (PD) profile of SNDX-6352 and durvalumab when given in combination in patients with advanced solid tumors.

  6. Phase 1b:Effect of SNDX-6352 when given in combination with a fixed dose of durvalumab on CSF-1 receptor occupancy. [ Time Frame: Approximately 6 months (from first dose to End of Treatment visit) ]
    To evaluate the change from Baseline in CSF-1 receptor occupancy (RO).

  7. Phase 1b: Exploration of relationship between candidate biomarker results and anti-tumor activity of SNDX-6352 when given in combination with a fixed dose of durvalumab. [ Time Frame: Approximately 6 months (from first dose to End of Treatment visit) ]
    To investigate the relationship between candidate biomarkers (e.g., CSF-1, IL-34) and anti-tumor activity of SNDX-6352 when given in combination with a fixed dose of durvalumab.

  8. Phase 1b: Exploration of relationship between additional biomarkers and anti-tumor activity of SNDX-6352 when given in combination with a fixed dose of durvalumab. [ Time Frame: Approximately 6 months (from first dose to End of Treatment visit) ]
    To investigate the relationship between other biomarkers (e.g., tumor infiltrating lymphocytes, PD-L1, PD-1, PD-L2, circulating classical and non-classical CD-16 monocytes in blood) and anti-tumor activity of SNDX-6352 when given in combination with a fixed dose of durvalumab.

  9. Phase 1b: Characterization of relationship in change from baseline in CSF-1, IL-34, etc. with SNDX-6352 administered intravenously when given in combination with a fixed dose of durvalumab. [ Time Frame: Approximately 6 months (from first dose to End of Treatment visit) ]
    To characterize the relationship in change from baseline in plasma colony stimulating factor-1 [CSF-1] interleukin-34 [IL-34]), and IFN-gamma, IL-1beta, IL-2, IL-4, IL-5, IL-6, CXCL8/IL-8, IL-10, IL-12 (p70), IL-13, TNF-alpha, CD204/206 and sCD163 with systemic PK of SNDX-6352 administered intravenously when given in combination with a fixed dose of durvalumab.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

Inclusion Criteria for Phase 1a and Phase 1b

Patients meeting all of the following criteria are considered eligible to participate in the study:

  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 enrollment.
  5. Has adequate organ and bone marrow function within 21 days before enrollment as defined below:

    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 institutional ULN.

    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 hysterectomy).
  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:

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 study drug.

    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 to:

    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 Pointes (TdP).
    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 treatment.
  7. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
  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 steroids
  17. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03238027


Contacts
Contact: Anthony Piscitelli 781-795-9426 apiscitelli@syndax.com
Contact: Sue Fischer 781-795-9419 sfischer@syndax.com

Locations
United States, Arizona
Honor Health Recruiting
Scottsdale, Arizona, United States, 85258
Contact: Sunil Sharma, MD    602-343-8445    ssharma@tgen.org   
United States, Maryland
Johns Hopkins University Recruiting
Baltimore, Maryland, United States, 21287
Contact: Nilofer Azad, MD       Nazad2@jhmi.edu   
United States, Oregon
Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Matthew Taylor, MD    503-494-3257    taylmatt@ohsu.edu   
United States, Texas
NEXT Oncology Recruiting
San Antonio, Texas, United States, 78229
Contact: Anthony Tolcher, MD    210-300-9044    atolcher@nextsat.com   
South Texas Accelerated Research Therapeutics Recruiting
San Antonio, Texas, United States, 78229
Contact: Drew W Rasco, MD    210-593-5250    Drew.Rasco@startsa.com   
Sponsors and Collaborators
Syndax Pharmaceuticals
Investigators
Study Director: Michael Meyers, MD Syndax Pharmaceuticals, Inc.

Responsible Party: Syndax Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03238027     History of Changes
Other Study ID Numbers: SNDX-6352-0502
First Posted: August 3, 2017    Key Record Dates
Last Update Posted: November 29, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Syndax Pharmaceuticals:
SNDX-6352
CSF-1R inhibitor
Colony Stimulating factor 1 receptor inhibitor
Solid Tumor
Recurrent locally advanced tumor
unresectable solid tumor
Metastatic tumor
durvalumab

Additional relevant MeSH terms:
Neoplasms
Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs