Study of SP-3164 in Relapsed or Refractory Non-Hodgkin's Lymphoma

Trial Title: Study of SP-3164 in Relapsed or Refractory Non-Hodgkin's Lymphoma

NCT ID: NCT05979857

Condition: Lymphoma, Non-Hodgkin's, Adult

Conditions: Official terms:
Lymphoma
Lymphoma, Non-Hodgkin

Study type: Interventional

Study phase: Early Phase 1

Overall status: Not yet recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Sequential Assignment

Intervention model description: This study is a phase 1, open-label, multicenter, dose escalation (part 1) and dose selection optimization (part 2) study of SP-3164 in patients with R/R B-cell NHL.

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: SP-3164
Description: SP-3164, an oral next generation cereblon-binding molecular glue 'protein degrader'
Arm group label: Dose Escalation
Arm group label: Dose Optimization

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.

Criteria for 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 Ability to take orally administered medication Washout period prior to Cycle 1 Day 1 of SP-3164: at least 21 days or 5 half-lives (whichever is shorter) from prior systemic anticancer treatment, including chemotherapy, biologic therapy, small molecule inhibitors, monoclonal antibodies, and any investigational agents; at least 14 days from palliative radiotherapy if ≤ 10 fractions or total dose ≤ 30 gray (Gy) or at least 28 days from radiotherapy if total dose > 30 Gy; at least 21 days from major surgery Life expectancy of at least 3 months 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 Malignant disease, other than that being treated in this study. Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) who have undergone potentially curative therapy are not excluded. Other exceptions include malignancies that were treated curatively and have not recurred within 3 years prior to Cycle 1 Day 1 and any malignancy considered indolent and that has never required therapy Other concurrent severe or uncontrolled concomitant medical conditions that might cause unacceptable safety risks or compromise compliance with the protocol Pregnant and breastfeeding women Known history of HIV-positivity; known hepatitis B or hepatitis C virus infection Men and women of child-bearing potential unwilling to use adequate contraception according to study protocol

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Start date: March 15, 2024

Completion date: August 15, 2027

Lead sponsor:
Agency: Salarius Pharmaceuticals, LLC
Agency class: Industry

Source: Salarius Pharmaceuticals, LLC

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05979857