A Phase 1, Open-label, Multicenter, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SP-3164 in Patients With Relapsed/Refractory Non-Hodgkin's Lymphoma
Overview
- Phase
- Early Phase 1
- Intervention
- SP-3164
- Conditions
- Lymphoma, Non-Hodgkin's, Adult
- Sponsor
- Salarius Pharmaceuticals, LLC
- Enrollment
- 72
- Primary Endpoint
- Dose Escalation: Characterize the Safety of SP-3164
- Status
- Not yet recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
The purpose of this research is to help researchers find out if SP-3164 is safe and if it may be of benefit in the treatment of patients with Non-Hodgkin's lymphoma that has progressed after prior treatment, or that never responded to previous treatment.
Detailed Description
SALA-003-NHL is a phase 1 open-label, multicenter, first-in-human study of SP-3164 in patients with R/R B-cell NHL that will be conducted in two parts. Part 1 is a dose escalation using a sequential accelerated titration design for the first two dose levels followed by a 3+3 dose escalation design to assess the safety and tolerability of SP-3164 in patients with R/R B-cell NHL. Upon completion of the dose escalation design and review of all available safety, tolerability, PK, PD, and preliminary efficacy data the Safety Review Committee (SRC) will recommend two dose levels for the randomized dose selection optimization (Part 2). The dose selection optimization will randomize 1:1 approximately 30 patients with R/R DLBCL to the two selected dose levels (15 new patients per dose level) to determine the recommended phase 2 dose (RP2D) and further characterize safety, tolerability, PK, PD, and preliminary efficacy data of SP-3164. SP-3164 will be administered orally once daily under fasting conditions on 7 consecutive on-treatment days followed by 7 consecutive off-treatment days. One treatment cycle will be defined as 28 days.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Diagnosis (WHO 2016 criteria) of R/R B-cell NHL in dose escalation (part 1) and limited to R/R DLBCL in dose selection optimization (part 2) confirmed by biopsy and immunophenotyping
- •Dose escalation: at time of enrollment, R/R B-cell NHL patients per WHO 2016 criteria including DLBCL (including low grade transformed lymphoma), mantle cell lymphoma, follicular lymphoma, and marginal zone lymphoma and must:
- •require treatment in the opinion of the Investigator
- •received at least 2 lines of systemic therapy for B-cell NHL
- •Dose selection optimization: at time of enrollment, R/R DLBCL (including low grade transformed lymphoma) patients must have received 2 or 3 lines of systemic therapy for DLBCL
- •o Prior immunomodulatory imide drug (IMiD) therapy is allowed (e.g., lenalidomide)
- •Measurable disease per the 2017 International Working Group Consensus Response Evaluation Criteria for Lymphoma
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- •Existing archival tumor tissue (fresh frozen paraffin embedded \[FFPE\], 5 unstained slides) not older than 2 years from Cycle 1 Day 1 or willingness to provide fresh tumor biopsy during screening
- •Normal organ and marrow function, defined by specific laboratory parameters
Exclusion Criteria
- •Patients with chronic lymphocytic leukemia, high grade B-cell lymphoma, or Richter's syndrome
- •Patients who have not recovered to Grade 1 toxicity or baseline due to any previous anticancer therapy according to the NCI CTCAE v5.0, excluding Grade 2 alopecia. Lymphopenia ≤ Grade 2 is allowed
- •Patients with primary central nervous system (CNS) lymphoma or active CNS or meningeal lymphomatous involvement
- •Persistent diarrhea or malabsorption of ≥ Grade 2 despite medical management
- •Impaired cardiac function or clinically significant cardiac disease, including symptomatic congestive heart failure, left ventricular ejection fraction (LVEF) \< 50%, unstable angina pectoris or cardiac arrhythmias, baseline QTc (Fridericia) \> 450 milliseconds, long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, myocardial infarct within 6 months of study enrollment, clinically significant pericardial disease
- •Solid organ transplant recipient
- •Allogeneic stem cell transplantation (SCT) recipient
- •Autologous SCT recipient \<100 days from Cycle 1 Day 1 or otherwise not fully recovered from SCT-related toxicity
- •Completion of CAR-T therapy \< 90 days from Cycle 1 Day 1
- •Systemic immunosuppressants and chronic systemic corticosteroids (at doses ≥ 10 mg/day of prednisone or equivalent) are prohibited
Arms & Interventions
Dose Escalation
For part 1 dose escalation, one patient per dose cohort will be initially recruited (accelerated titration dose-escalation, single-patient cohorts/dose level) for the first two dose levels or until the first instance of a ≥ Grade 2 toxicity (excluding Grade 2 neutropenia and lymphopenia and adverse events unequivocally due to the underlying disease or to an extraneous cause), or dose-limiting toxicity (DLT), whichever occurs earlier. Further cohorts will be recruited in blocks of three patients, i.e., 3+3 dose escalation design.
Intervention: SP-3164
Dose Optimization
For part 2 dose selection optimization, two dose levels will be selected by the Safety Review Committee (SRC) based on review of all available data on safety, tolerability, PK, PD, and preliminary efficacy from part 1. The dose selection optimization will include only patients with R/R DLBCL and will randomize 1:1 approximately 30 new patients at the two selected dose levels (15 patients to each of the two selected dose levels) before declaring the RP2D. Assessment of PK/PD of SP-3164 will be included in part 2 dose selection optimization.
Intervention: SP-3164
Outcomes
Primary Outcomes
Dose Escalation: Characterize the Safety of SP-3164
Time Frame: 4 months
Dose Escalation (Part 1) • To characterize the safety, dose limiting toxicities (DLTs), and maximum tolerated dose (MTD) of SP-3164
Dose Escalation: Assess Dose Limiting Toxicities of SP-3164
Time Frame: 6 months
Dose Escalation (Part 1) • To characterize the safety, dose limiting toxicities (DLTs), and maximum tolerated dose (MTD) of SP-3164
Dose Escalation: Assess the Maximum Tolerated Dose of SP-3164
Time Frame: 6 months
Dose Escalation (Part 1) • To characterize the safety, dose limiting toxicities (DLTs), and maximum tolerated dose (MTD) of SP-3164
Dose Optimization: Further characterize the safety of the 2 selected doses of SP-3164 from Part 1 (dose escalation)
Time Frame: 6 months
Dose Selection Optimization (Part 2) • To further characterize the safety of the two selected doses of SP-3164 from part 1 and determine the recommended phase 2 dose (RP2D) of SP-3164 for future studies
Dose Optimization: Determine the recommended phase 2 dose of SP-3164 for future studies
Time Frame: 6 months
• To further characterize the safety of the two selected doses of SP-3164 from part 1 and determine the recommended phase 2 dose (RP2D) of SP-3164 for future studies