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

NCT05979857 | Not Yet Recruiting Early Phase 1 FDA Drug

• 1 other identifier: SALA-003-NHL
• Study Type: interventional
• Target: 72
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Lymphoma, Non-Hodgkin's, Adult

Outcome Measures

Primary Outcomes (5)

• Dose Escalation: Characterize the Safety of SP-3164

  Dose Escalation (Part 1) • To characterize the safety, dose limiting toxicities (DLTs), and maximum tolerated dose (MTD) of SP-3164

  4 months

• Dose Escalation: Assess Dose Limiting Toxicities of SP-3164

  Dose Escalation (Part 1) • To characterize the safety, dose limiting toxicities (DLTs), and maximum tolerated dose (MTD) of SP-3164

  6 months

• Dose Escalation: Assess the Maximum Tolerated Dose of SP-3164

  Dose Escalation (Part 1) • To characterize the safety, dose limiting toxicities (DLTs), and maximum tolerated dose (MTD) of SP-3164

  6 months

• Dose Optimization: Further characterize the safety of the 2 selected doses of SP-3164 from Part 1 (dose escalation)

  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

  6 months

• Dose Optimization: Determine the recommended phase 2 dose of SP-3164 for future studies

  • 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

  6 months

Study Arms (2)

Dose Escalation

EXPERIMENTAL

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.

Drug: SP-3164

Dose Optimization

EXPERIMENTAL

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.

Drug: SP-3164

Interventions

SP-3164 DRUG

SP-3164, an oral next generation cereblon-binding molecular glue 'protein degrader'

Dose Escalation; Dose Optimization

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Salarius Pharmaceuticals, LLC: lead

MeSH Terms

Conditions

Lymphoma

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Rebecca Griffith-Eskew

CONTACT

+1 254 265 2782; reskew@salariuspharma.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 31, 2023
• First Posted: August 7, 2023
• Study Start: March 15, 2024
• Primary Completion: August 15, 2025
• Study Completion (Estimated): August 15, 2027
• Last Updated: November 22, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share