Chronic Graft-versus-host-disease
Conditions
Keywords
cGVHD
Brief summary
This is a Phase 1/2, Open-label, Dose Escalation study to investigate axatilimab in participants with active chronic graft versus host disease (cGVHD).
Detailed description
This is a dose escalation and dose expansion study in participants with active cGVHD who have received at least 2 lines of prior therapy.
Interventions
DRUGaxatilimab
axatilimab is a high affinity antibody targeting the colony stimulating factor 1 receptor (CSF-1R). CSF-1R signaling has been demonstrated in nonclinical studies to be the key regulatory pathway involved in the expansion and infiltration of donor derived macrophages that mediate the disease processes involved in cGVHD.
Sponsors
Syndax Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The dose-escalation phase is a sequential group (dose-escalating) treatment study that is open-label. The dose-expansion phase is a parallel group treatment study with open-label cohorts.
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Participant must be 6 years of age or older, at the time of signing the informed consent. 2. Participants who are allogeneic hematopoietic stem cell transplant (HSCT) recipients with cGVHD requiring systemic immune suppression. 3. Participants with active cGVHD who have received at least 2 lines of therapy. Participants 18 or older with active cGVHD who have erythematous rash involving \>25% body surface area or a NIH mouth score of \>4 must have received prior ibrutinib therapy. a. Active cGVHD is defined as the presence of signs and symptoms of cGVHD per 2014 NIH Consensus Development Project on Criteria for Clinical trials in cGVHD. 4. Participants may have persistent active acute and cGVHD manifestations (overlap syndrome), as defined by 2014 NIH Consensus Development Project on Criteria for Clinical trials in cGVHD. 5. Karnofsky Performance Scale of ≥60 with a life expectancy of at least 3 months (if aged 16 years or older); Lansky Performance Score of ≥60 (if less than 16 years). 6. Adequate organ and bone marrow functions. 7. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 8. Capable of giving signed informed consent which includes compliance with the study requirements and restrictions. Key
Exclusion criteria
1. Has acute GVHD without manifestations of cGVHD. 2. Any evidence (histologic, cytogenetic, molecular, hematologic, or mixed) of relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening. 3. History or other evidence of severe illness, uncontrolled infection or any other conditions that would make the participant, in the opinion of the Investigator, unsuitable for the study. 4. Known history of human immunodeficiency virus (HIV) or active hepatitis C virus (HCV) or hepatitis B virus (HBV). 5. Diagnosed with another malignancy (other than malignancy for which transplant was performed) within 3 years of enrollment, unless previously treated with curative intent and must be approved by Sponsor medical monitor (for example, completely resected basal cell or squamous cell carcinoma of the skin, resected in situ cervical malignancy, resected breast ductal carcinoma in situ, or low-risk prostate cancer after curative resection). 6. Female participants who are pregnant or breastfeeding. 7. Previous exposure to study intervention or known allergy/sensitivity to study intervention. 8. Taking agents other than a corticosteroid and one calcineurin inhibitor (CNI) for treatment of cGVHD (This does not include agents being prescribed expressly for the treatment of acute GVHD). 9. Receiving an investigational treatment within 28 days of study entry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of Participants With DLTs | Day 1 through the first 28 days from the first dose of SNDX-6352 or administration of the third dose (Cycle 2 Day 1), whichever is later (from Cycle 1 Day 1 to Cycle 2 Day 1) | A DLT was defined as the occurrence of any protocol-specified event within the first 28 days from the first dose of SNDX-6352 or administration of the third dose (Cycle 2 Day 1), whichever is later (from Cycle 1 Day 1 to Cycle 2 Day 1) and assessed by the Investigator as not being definitely attributable to underlying disease, disease progression, inter-current illness, concomitant medications or any other alternative cause. |
| Phase 1: Recommended Phase 2 Dose (RP2D) | Day 1 through the first 28 days from the first dose of SNDX-6352 or administration of the third dose (Cycle 2 Day 1), whichever is later (from C1D1 to C2D1) | The RP2D was determined in discussion with the Sponsor, Medical Monitor, and Dose Determination Phase Investigators and was based on observations from the Phase 1 of the study (clinical benefit in chronic graft versus host disease \[cGVHD\] and pharmacokinetic/pharmacodynamic effects). |
| Phase 2: Overall Response Rate (ORR) as Assessed by the Number of Participants With Complete Response (CR) or Partial Response (PR) at Cycle 7 Day 1 (Day 168) | Cycle 7 Day 1 (Day 168) | CR or PR was defined by the 2014 National Institutes of Health (NIH) Consensus Development Project on Criteria for Clinical Trials in cGVHD.CR was defined as resolution of all manifestations in each organ or site, and PR was defined as improvement in at least 1 organ or site without progression in any other organ or site. ORR was defined as the percentage of participants achieving a best overall response of CR or PR .ORR calculated as: (number of participants with best overall response as CR or PR)/total number of participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | Baseline, Cycle 1 Day 8, Day 15, predose at Cycle 2 Day 1, Cycle 4 Day 1 (28-day cycles), and end of treatment (EOT) (median duration of treatment = 7 months) | Blood samples were collected for determination of serum concentrations. |
| Phase 1: Percent Change From Baseline in Nonclassical Monocytes (CD14+CD16++) | Baseline, Day 8, Day 15, predose at Cycle 2 Day 1, Cycle 4 Day 1, and EOT (median duration of treatment = 7 months) | Blood samples were collected for determination nonclassical monocytes levels. |
| Phase 1: Number of Participants Positive for Anti-Drug Antibodies (ADA) | Predose on Cycle 1 Day 1, Cycle 1 Day 15, Cycle 3 Day 1, Day 1 of each subsequent cycle through EOT plus 30 days after last dose (safety follow-up) (median duration of treatment = 7 months) | Blood samples were collected for ADA assessment. A participant was considered ADA positive if at least 1 postbaseline sample was ADA positive. |
| Phase 2: Best Overall Response (BOR), as Defined by the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD | Day 1 of each 28-Day cycle up to Cycle 7 Day 1 | Physician-reported global cGVHD activity assessment and cGVHD response determination. Best overall response was calculated as percent of participants with a response of CR or PR. |
| Phase 2: Failure Free Survival (FFS) | From first dose of study intervention (Day 1) up to 27 months | FFS was defined as the time from first dose of study intervention to unequivocal progression of cGVHD or relapse of underlying malignancy or addition of another systemic immune suppressive therapy or discontinuation of study treatment due to toxicity or death for any reason. Unequivocal progression of cGVHD is defined as treatment discontinuation due to clinical progression. The duration of FFS was evaluated using organ-specific cGVHD activity assessment form and and summarized descriptively using the Kaplan-Meier method. |
| Phase 2: Duration of Response (DOR) | Day 1 of each 28-Day cycle for up to 12 cycles | DOR was defined as the time of initial response until documented progression or start of another systemic treatment as assessed by the Kaplan-Meir method. |
| Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration for SNDX-6352 | Cycle 1: predose, at 30 min (end of infusion), and at 1 hour and 8 hours on Day 1 and Day 15 | Blood samples were collected for determination of SNDX-6352 concentration. |
| Phase 2: Organ-specific Response Rate Based on 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD | Day 1 of each 28-Day cycle for up to 12 cycles | The percentage of participants with a response (CR/PR) in the skin, eyes, mouth, esophagus, upper gastrointestinal (GI), lower GI, liver, lungs, or joints and fascia were assessed using the NIH Consensus Development Project on Clinical Trials. |
| Phase 2: Number of Participants With a Joint and Fascia Response Based on Refined NIH Response Algorithm for cGVHD | Day 1 of each 28-Day cycle for up to 12 cycles | — |
| Phase 2: Number of Participants With A Lee Symptom Scale Summary Score Decrease of at Least 7 Points From Baseline | Day 1 of each 28-Day cycle for up to 12 cycles | The Lee cGVHD symptom questionnaire asked participants to indicate the degree of bother that they experienced during the past 7 days due to symptoms in 7 domains potentially affected by chronic GVHD (skin, eyes and mouth, breathing, eating and digestion, muscles and joints, energy, emotional distress) using a 5-point Likert scale from 0 not at all to 4 extremely. Scores were normalized (0 to 100 scale) and the number of participants with a ≥ 7-point decrease in normalized score was calculated. A decrease in score indicated improvement in symptoms. |
| Phase 2: Number of Participants With a ≥50% Reduction in Prednisone Equivalent Dosage Lasting at Least 28 Days | Day 1 of each 28-Day cycle for up to 12 cycles | — |
| Phase 2: Number of Participants Who Discontinued Calcineurin Inhibitor Use | Day 1 of each 28-Day cycle for up to 12 cycles | — |
| Phase 2: Sustained Response Rate (SRR) | Day 1 of each 28-Day cycle for up to 12 cycles | SSR of CR or PR ≥20 weeks was defined as rate of CR or PR lasting for at least 20 weeks from the time of initial response. |
| Phase 1: Observed Maximum Plasma Concentration for SNDX-6352 | Cycle 1: predose, at 30 min (end of infusion), and at 1 hour and 8 hours on Day 1 and Day 15 | Blood samples were collected for determination of SNDX-6352 concentration. |
| Phase 1: Time to Observed Maximum Plasma Concentration | Cycle 1: predose, at 30 min (end of infusion), and at 1 hour and 8 hours on Day 1 and Day 15 | Blood samples were collected for determination of SNDX-6352 concentration. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg Q2W Participants received an IV infusion of SNDX-6352 at 0.15 mg/kg Q2W. | 1 |
| Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg Q2W Participants received an IV infusion of SNDX-6352 0.5 mg/kg Q2W. | 1 |
| Phase 1 Dose Escalation: SNDX-6352 1 mg/kg Q2W Participants received an IV infusion of SNDX-6352 1 mg/kg Q2W. | 3 |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q2W Participants received an IV infusion of SNDX-6352 3 mg/kg Q2W. | 6 |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q4W Participants received an IV infusion of SNDX-6352 3 mg/kg Q4W. | 6 |
| Phase 2 Dose Expansion: SNDX-6352 1 mg/kg Q2W Participants received an IV infusion of SNDX-6352 1 mg/kg Q2W. | 23 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Difficulty Coming into Site | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Drug Intolerance | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Investigator's Decision | 0 | 0 | 0 | 1 | 0 | 7 |
| Overall Study | Noncompliance with follow-up visit | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Not Treated | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Progressive Disease | 1 | 0 | 1 | 0 | 3 | 4 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Total | Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg Q2W | Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg Q2W | Phase 1 Dose Escalation: SNDX-6352 1 mg/kg Q2W | Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q2W | Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q4W | Phase 2 Dose Expansion: SNDX-6352 1 mg/kg Q2W |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 54.7 years | 64.0 years | 48.0 years | 43.7 years | 61.0 years | 59.2 years | 52.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 1 Participants | 1 Participants | 3 Participants | 6 Participants | 6 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Black or African American | 5 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 34 Participants | 0 Participants | 1 Participants | 3 Participants | 5 Participants | 5 Participants | 20 Participants |
| Sex: Female, Male Female | 15 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 2 Participants | 9 Participants |
| Sex: Female, Male Male | 25 Participants | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 4 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 | 1 / 26 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 26 / 26 | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 1 / 1 | 1 / 1 | 12 / 26 | 3 / 6 | 2 / 6 |
Outcome results
Primary
Phase 1: Number of Participants With DLTs
A DLT was defined as the occurrence of any protocol-specified event within the first 28 days from the first dose of SNDX-6352 or administration of the third dose (Cycle 2 Day 1), whichever is later (from Cycle 1 Day 1 to Cycle 2 Day 1) and assessed by the Investigator as not being definitely attributable to underlying disease, disease progression, inter-current illness, concomitant medications or any other alternative cause.
Time frame: Day 1 through the first 28 days from the first dose of SNDX-6352 or administration of the third dose (Cycle 2 Day 1), whichever is later (from Cycle 1 Day 1 to Cycle 2 Day 1)
Population: Participants who received at least 1 cycle of treatment and had at least one post-baseline response assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 1: Number of Participants With DLTs | 0 Participants |
| Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg | Phase 1: Number of Participants With DLTs | 0 Participants |
| Phase 1 Dose Escalation: SNDX-6352 1 mg/kg | Phase 1: Number of Participants With DLTs | 0 Participants |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg | Phase 1: Number of Participants With DLTs | 2 Participants |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q4W | Phase 1: Number of Participants With DLTs | 0 Participants |
Primary
Phase 1: Recommended Phase 2 Dose (RP2D)
The RP2D was determined in discussion with the Sponsor, Medical Monitor, and Dose Determination Phase Investigators and was based on observations from the Phase 1 of the study (clinical benefit in chronic graft versus host disease \[cGVHD\] and pharmacokinetic/pharmacodynamic effects).
Time frame: Day 1 through the first 28 days from the first dose of SNDX-6352 or administration of the third dose (Cycle 2 Day 1), whichever is later (from C1D1 to C2D1)
Population: Participants who received at least 1 cycle of treatment and had at least one post-baseline response assessment in Phase 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 1: Recommended Phase 2 Dose (RP2D) | 1 mg/kg |
Primary
Phase 2: Overall Response Rate (ORR) as Assessed by the Number of Participants With Complete Response (CR) or Partial Response (PR) at Cycle 7 Day 1 (Day 168)
CR or PR was defined by the 2014 National Institutes of Health (NIH) Consensus Development Project on Criteria for Clinical Trials in cGVHD.CR was defined as resolution of all manifestations in each organ or site, and PR was defined as improvement in at least 1 organ or site without progression in any other organ or site. ORR was defined as the percentage of participants achieving a best overall response of CR or PR .ORR calculated as: (number of participants with best overall response as CR or PR)/total number of participants.
Time frame: Cycle 7 Day 1 (Day 168)
Population: Safety Analysis Set: All participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 2: Overall Response Rate (ORR) as Assessed by the Number of Participants With Complete Response (CR) or Partial Response (PR) at Cycle 7 Day 1 (Day 168) | 39.1 percentage of participants |
Secondary
Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration for SNDX-6352
Blood samples were collected for determination of SNDX-6352 concentration.
Time frame: Cycle 1: predose, at 30 min (end of infusion), and at 1 hour and 8 hours on Day 1 and Day 15
Population: Pharmacokinetic Analysis Set: All treated participants who had at least 1 plasma concentration measured. Number Analyzed = participants who were evaluable at specified timepoints
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration for SNDX-6352 | Cycle 1 Day 15 | 22.9 µg*h/mL |
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration for SNDX-6352 | Cycle 1 Day 1 | 30.7 µg*h/mL |
| Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg | Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration for SNDX-6352 | Cycle 1 Day 15 | 98.9 µg*h/mL |
| Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg | Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration for SNDX-6352 | Cycle 1 Day 1 | 96.2 µg*h/mL |
| Phase 1 Dose Escalation: SNDX-6352 1 mg/kg | Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration for SNDX-6352 | Cycle 1 Day 1 | 1546.0 µg*h/mL |
| Phase 1 Dose Escalation: SNDX-6352 1 mg/kg | Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration for SNDX-6352 | Cycle 1 Day 15 | 714.0 µg*h/mL |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg | Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration for SNDX-6352 | Cycle 1 Day 15 | 14,055.0 µg*h/mL |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg | Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration for SNDX-6352 | Cycle 1 Day 1 | 10263.3 µg*h/mL |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q4W | Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration for SNDX-6352 | Cycle 1 Day 1 | 12256.7 µg*h/mL |
Secondary
Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations
Blood samples were collected for determination of serum concentrations.
Time frame: Baseline, Cycle 1 Day 8, Day 15, predose at Cycle 2 Day 1, Cycle 4 Day 1 (28-day cycles), and end of treatment (EOT) (median duration of treatment = 7 months)
Population: Safety Analysis Set: All participants who received at least 1 dose of study treatment. Number Analyzed = participants who were evaluable at specified timepoints
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | CSF-1 Cycle 2 Day 1 | 19.0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | CSF-1 Cycle 1 Day 15 | 69.0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | CSF-1 Cycle 1 Day 8 | 2.0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | CSF-1 EOT | 63.0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | IL-34 Cycle 1 Day 8 | 0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | IL-34 Cycle 1 Day 15 | 0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | IL-34 Cycle 2 Day 1 | 0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | IL-34 EOT | 0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | IL-34 Cycle 2 Day 1 | 0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | IL-34 Cycle 4 Day 1 | 0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | IL-34 Cycle 1 Day 15 | 0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | CSF-1 Cycle 1 Day 15 | -87.0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | CSF-1 Cycle 1 Day 8 | 602.0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | CSF-1 Cycle 2 Day 1 | 227.0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | IL-34 Cycle 1 Day 8 | 0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | CSF-1 Cycle 4 Day 1 | 229.0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 1 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | IL-34 Cycle 1 Day 8 | 156.7 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 1 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | IL-34 Cycle 2 Day 1 | 0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 1 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | IL-34 Cycle 1 Day 15 | 0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 1 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | CSF-1 Cycle 1 Day 15 | 680.0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 1 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | CSF-1 Cycle 4 Day 1 | 465.0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 1 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | CSF-1 Cycle 1 Day 8 | 364480.0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 1 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | IL-34 Cycle 4 Day 1 | 0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 1 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | CSF-1 Cycle 2 Day 1 | 400.0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | CSF-1 Cycle 1 Day 15 | 897522.0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | CSF-1 Cycle 2 Day 1 | 1474438.5 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | CSF-1 Cycle 4 Day 1 | 899337.5 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | IL-34 Cycle 4 Day 1 | 569.4 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | IL-34 Cycle 1 Day 8 | 576.2 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | IL-34 Cycle 1 Day 15 | 690.7 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | IL-34 Cycle 2 Day 1 | 1133.7 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | CSF-1 Cycle 1 Day 8 | 544837.5 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q4W | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | IL-34 Cycle 4 Day 1 | 533.7 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q4W | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | IL-34 Cycle 1 Day 8 | 286.7 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q4W | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | CSF-1 Cycle 2 Day 1 | 773476.0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q4W | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | CSF-1 EOT | 1709787.0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q4W | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | CSF-1 Cycle 4 Day 1 | 1386196.5 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q4W | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | CSF-1 Cycle 1 Day 15 | 821180.5 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q4W | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | CSF-1 Cycle 1 Day 8 | 451482.0 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q4W | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | IL-34 Cycle 2 Day 1 | 190.7 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q4W | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | IL-34 Cycle 1 Day 15 | 456.7 pg/mL |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q4W | Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations | IL-34 EOT | 676.7 pg/mL |
Secondary
Phase 1: Number of Participants Positive for Anti-Drug Antibodies (ADA)
Blood samples were collected for ADA assessment. A participant was considered ADA positive if at least 1 postbaseline sample was ADA positive.
Time frame: Predose on Cycle 1 Day 1, Cycle 1 Day 15, Cycle 3 Day 1, Day 1 of each subsequent cycle through EOT plus 30 days after last dose (safety follow-up) (median duration of treatment = 7 months)
Population: Safety Analysis Set: All participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 1: Number of Participants Positive for Anti-Drug Antibodies (ADA) | 0 Participants |
| Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg | Phase 1: Number of Participants Positive for Anti-Drug Antibodies (ADA) | 0 Participants |
| Phase 1 Dose Escalation: SNDX-6352 1 mg/kg | Phase 1: Number of Participants Positive for Anti-Drug Antibodies (ADA) | 1 Participants |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg | Phase 1: Number of Participants Positive for Anti-Drug Antibodies (ADA) | 3 Participants |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q4W | Phase 1: Number of Participants Positive for Anti-Drug Antibodies (ADA) | 2 Participants |
Secondary
Phase 1: Observed Maximum Plasma Concentration for SNDX-6352
Blood samples were collected for determination of SNDX-6352 concentration.
Time frame: Cycle 1: predose, at 30 min (end of infusion), and at 1 hour and 8 hours on Day 1 and Day 15
Population: Pharmacokinetic Analysis Set: All treated participants who had at least 1 plasma concentration measured. Number Analyzed = participants who were evaluable at specified timepoints
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 1: Observed Maximum Plasma Concentration for SNDX-6352 | Cycle 1 Day 1 | 4.6 µg/mL |
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 1: Observed Maximum Plasma Concentration for SNDX-6352 | Cycle 1 Day 15 | 3.5 µg/mL |
| Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg | Phase 1: Observed Maximum Plasma Concentration for SNDX-6352 | Cycle 1 Day 15 | 14.2 µg/mL |
| Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg | Phase 1: Observed Maximum Plasma Concentration for SNDX-6352 | Cycle 1 Day 1 | 13.7 µg/mL |
| Phase 1 Dose Escalation: SNDX-6352 1 mg/kg | Phase 1: Observed Maximum Plasma Concentration for SNDX-6352 | Cycle 1 Day 15 | 27.4 µg/mL |
| Phase 1 Dose Escalation: SNDX-6352 1 mg/kg | Phase 1: Observed Maximum Plasma Concentration for SNDX-6352 | Cycle 1 Day 1 | 26.7 µg/mL |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg | Phase 1: Observed Maximum Plasma Concentration for SNDX-6352 | Cycle 1 Day 15 | 91.8 µg/mL |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg | Phase 1: Observed Maximum Plasma Concentration for SNDX-6352 | Cycle 1 Day 1 | 84.0 µg/mL |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q4W | Phase 1: Observed Maximum Plasma Concentration for SNDX-6352 | Cycle 1 Day 1 | 82.2 µg/mL |
Secondary
Phase 1: Percent Change From Baseline in Nonclassical Monocytes (CD14+CD16++)
Blood samples were collected for determination nonclassical monocytes levels.
Time frame: Baseline, Day 8, Day 15, predose at Cycle 2 Day 1, Cycle 4 Day 1, and EOT (median duration of treatment = 7 months)
Population: Safety Analysis Set: All participants who received at least 1 dose of study treatment. Number Analyzed = participants who were evaluable at specified timepoints
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg | Phase 1: Percent Change From Baseline in Nonclassical Monocytes (CD14+CD16++) | Cycle 1 Day 8 | -41.7 percent change |
| Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg | Phase 1: Percent Change From Baseline in Nonclassical Monocytes (CD14+CD16++) | Cycle 1 Day 15 | -66.7 percent change |
| Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg | Phase 1: Percent Change From Baseline in Nonclassical Monocytes (CD14+CD16++) | Cycle 2 Day 1 | -58.3 percent change |
| Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg | Phase 1: Percent Change From Baseline in Nonclassical Monocytes (CD14+CD16++) | Cycle 4 Day 1 | -16.7 percent change |
| Phase 1 Dose Escalation: SNDX-6352 1 mg/kg | Phase 1: Percent Change From Baseline in Nonclassical Monocytes (CD14+CD16++) | Cycle 4 Day 1 | 273.5 percent change |
| Phase 1 Dose Escalation: SNDX-6352 1 mg/kg | Phase 1: Percent Change From Baseline in Nonclassical Monocytes (CD14+CD16++) | Cycle 2 Day 1 | -31.0 percent change |
| Phase 1 Dose Escalation: SNDX-6352 1 mg/kg | Phase 1: Percent Change From Baseline in Nonclassical Monocytes (CD14+CD16++) | Cycle 1 Day 15 | 242.8 percent change |
| Phase 1 Dose Escalation: SNDX-6352 1 mg/kg | Phase 1: Percent Change From Baseline in Nonclassical Monocytes (CD14+CD16++) | Cycle 1 Day 8 | -92.7 percent change |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg | Phase 1: Percent Change From Baseline in Nonclassical Monocytes (CD14+CD16++) | Cycle 4 Day 1 | -76.5 percent change |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg | Phase 1: Percent Change From Baseline in Nonclassical Monocytes (CD14+CD16++) | Cycle 1 Day 15 | -96.5 percent change |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg | Phase 1: Percent Change From Baseline in Nonclassical Monocytes (CD14+CD16++) | Cycle 2 Day 1 | -94.4 percent change |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg | Phase 1: Percent Change From Baseline in Nonclassical Monocytes (CD14+CD16++) | Cycle 1 Day 8 | -95.7 percent change |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q4W | Phase 1: Percent Change From Baseline in Nonclassical Monocytes (CD14+CD16++) | Cycle 2 Day 1 | -67.5 percent change |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q4W | Phase 1: Percent Change From Baseline in Nonclassical Monocytes (CD14+CD16++) | EOT | -75.0 percent change |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q4W | Phase 1: Percent Change From Baseline in Nonclassical Monocytes (CD14+CD16++) | Cycle 1 Day 22 | -90.9 percent change |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q4W | Phase 1: Percent Change From Baseline in Nonclassical Monocytes (CD14+CD16++) | Cycle 1 Day 15 | -81.5 percent change |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q4W | Phase 1: Percent Change From Baseline in Nonclassical Monocytes (CD14+CD16++) | Cycle 4 Day 1 | -82.5 percent change |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q4W | Phase 1: Percent Change From Baseline in Nonclassical Monocytes (CD14+CD16++) | Cycle 1 Day 8 | -81.4 percent change |
Secondary
Phase 1: Time to Observed Maximum Plasma Concentration
Blood samples were collected for determination of SNDX-6352 concentration.
Time frame: Cycle 1: predose, at 30 min (end of infusion), and at 1 hour and 8 hours on Day 1 and Day 15
Population: Pharmacokinetic Analysis Set: All treated participants who had at least 1 plasma concentration measured. Number Analyzed = participants who were evaluable at specified timepoints
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 1: Time to Observed Maximum Plasma Concentration | Cycle 1 Day 1 | 1.0 hours |
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 1: Time to Observed Maximum Plasma Concentration | Cycle 1 Day 15 | 0.6 hours |
| Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg | Phase 1: Time to Observed Maximum Plasma Concentration | Cycle 1 Day 15 | 0.5 hours |
| Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg | Phase 1: Time to Observed Maximum Plasma Concentration | Cycle 1 Day 1 | 1.5 hours |
| Phase 1 Dose Escalation: SNDX-6352 1 mg/kg | Phase 1: Time to Observed Maximum Plasma Concentration | Cycle 1 Day 15 | 1.0 hours |
| Phase 1 Dose Escalation: SNDX-6352 1 mg/kg | Phase 1: Time to Observed Maximum Plasma Concentration | Cycle 1 Day 1 | 0.6 hours |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg | Phase 1: Time to Observed Maximum Plasma Concentration | Cycle 1 Day 15 | 1.0 hours |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg | Phase 1: Time to Observed Maximum Plasma Concentration | Cycle 1 Day 1 | 0.9 hours |
| Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q4W | Phase 1: Time to Observed Maximum Plasma Concentration | Cycle 1 Day 1 | 1.0 hours |
Secondary
Phase 2: Best Overall Response (BOR), as Defined by the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD
Physician-reported global cGVHD activity assessment and cGVHD response determination. Best overall response was calculated as percent of participants with a response of CR or PR.
Time frame: Day 1 of each 28-Day cycle up to Cycle 7 Day 1
Population: Safety Analysis Set: All participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 2: Best Overall Response (BOR), as Defined by the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD | 78.3 percentage of participants |
Secondary
Phase 2: Duration of Response (DOR)
DOR was defined as the time of initial response until documented progression or start of another systemic treatment as assessed by the Kaplan-Meir method.
Time frame: Day 1 of each 28-Day cycle for up to 12 cycles
Population: Participants who achieved PR or CR in the study were evaluable for DOR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 2: Duration of Response (DOR) | 9.53 months |
Secondary
Phase 2: Failure Free Survival (FFS)
FFS was defined as the time from first dose of study intervention to unequivocal progression of cGVHD or relapse of underlying malignancy or addition of another systemic immune suppressive therapy or discontinuation of study treatment due to toxicity or death for any reason. Unequivocal progression of cGVHD is defined as treatment discontinuation due to clinical progression. The duration of FFS was evaluated using organ-specific cGVHD activity assessment form and and summarized descriptively using the Kaplan-Meier method.
Time frame: From first dose of study intervention (Day 1) up to 27 months
Population: Safety Analysis Set: All participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 2: Failure Free Survival (FFS) | 16.9 months |
Secondary
Phase 2: Number of Participants Who Discontinued Calcineurin Inhibitor Use
Time frame: Day 1 of each 28-Day cycle for up to 12 cycles
Population: Safety Analysis Set: All participants who received at least 1 dose of study treatment and had calcineurin inhibitors usage at Cycle 1 Day 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 2: Number of Participants Who Discontinued Calcineurin Inhibitor Use | 0 Participants |
Secondary
Phase 2: Number of Participants With a ≥50% Reduction in Prednisone Equivalent Dosage Lasting at Least 28 Days
Time frame: Day 1 of each 28-Day cycle for up to 12 cycles
Population: Safety Analysis Set: All participants who received at least 1 dose of study treatment and had corticosteroid usage at Cycle 1 Day 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 2: Number of Participants With a ≥50% Reduction in Prednisone Equivalent Dosage Lasting at Least 28 Days | 5 Participants |
Secondary
Phase 2: Number of Participants With a Joint and Fascia Response Based on Refined NIH Response Algorithm for cGVHD
Time frame: Day 1 of each 28-Day cycle for up to 12 cycles
Population: Safety Analysis Set: All participants who received at least 1 dose of study treatment and who had this assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 2: Number of Participants With a Joint and Fascia Response Based on Refined NIH Response Algorithm for cGVHD | Improved | 10 Participants |
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 2: Number of Participants With a Joint and Fascia Response Based on Refined NIH Response Algorithm for cGVHD | Stable | 7 Participants |
Secondary
Phase 2: Number of Participants With A Lee Symptom Scale Summary Score Decrease of at Least 7 Points From Baseline
The Lee cGVHD symptom questionnaire asked participants to indicate the degree of bother that they experienced during the past 7 days due to symptoms in 7 domains potentially affected by chronic GVHD (skin, eyes and mouth, breathing, eating and digestion, muscles and joints, energy, emotional distress) using a 5-point Likert scale from 0 not at all to 4 extremely. Scores were normalized (0 to 100 scale) and the number of participants with a ≥ 7-point decrease in normalized score was calculated. A decrease in score indicated improvement in symptoms.
Time frame: Day 1 of each 28-Day cycle for up to 12 cycles
Population: Safety Analysis Set: All participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 2: Number of Participants With A Lee Symptom Scale Summary Score Decrease of at Least 7 Points From Baseline | 12 Participants |
Secondary
Phase 2: Organ-specific Response Rate Based on 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD
The percentage of participants with a response (CR/PR) in the skin, eyes, mouth, esophagus, upper gastrointestinal (GI), lower GI, liver, lungs, or joints and fascia were assessed using the NIH Consensus Development Project on Clinical Trials.
Time frame: Day 1 of each 28-Day cycle for up to 12 cycles
Population: Safety Analysis Set: All participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 2: Organ-specific Response Rate Based on 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD | Mouth | 75.0 percentage of participants |
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 2: Organ-specific Response Rate Based on 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD | Esophagus | 83.3 percentage of participants |
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 2: Organ-specific Response Rate Based on 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD | Eyes | 18.8 percentage of participants |
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 2: Organ-specific Response Rate Based on 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD | Joints and Fascia | 76.5 percentage of participants |
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 2: Organ-specific Response Rate Based on 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD | Liver | 0 percentage of participants |
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 2: Organ-specific Response Rate Based on 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD | Lower GI | 100.0 percentage of participants |
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 2: Organ-specific Response Rate Based on 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD | Lungs | 33.3 percentage of participants |
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 2: Organ-specific Response Rate Based on 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD | Skin | 19.0 percentage of participants |
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 2: Organ-specific Response Rate Based on 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD | Upper GI | 100.0 percentage of participants |
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 2: Organ-specific Response Rate Based on 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD | Global | 47.8 percentage of participants |
Secondary
Phase 2: Sustained Response Rate (SRR)
SSR of CR or PR ≥20 weeks was defined as rate of CR or PR lasting for at least 20 weeks from the time of initial response.
Time frame: Day 1 of each 28-Day cycle for up to 12 cycles
Population: Safety Analysis Set: All participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg | Phase 2: Sustained Response Rate (SRR) | 39.1 percentage of participants |