Study of SNX281 in Subjects With Advanced Solid Tumors and Lymphoma

NCT04609579 | Terminated Phase 1 FDA Drug

• 3 other identifiers: SNX281-001MK-3475-D44KEYNOTE-D44
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 4

Brief Summary

This clinical trial is evaluating a drug called SNX281 given by itself and in combination with pembrolizumab (KEYTRUDA®) in participants with advanced solid tumors and lymphoma. The main goals of this study are to:

• Find the recommended dose of SNX281 that can be given to participants safely alone and in combination with pembrolizumab (KEYTRUDA®).
• Learn more about the side effects and safety profile of SNX281 alone and in combination with pembrolizumab (KEYTRUDA®)
• Learn more about pharmacological characteristics of SNX281 alone and in combination with pembrolizumab (KEYTRUDA®)
• Learn more about effectiveness of SNX281 alone and in combination with pembrolizumab (KEYTRUDA®)

Conditions

Advanced Solid Tumor; Advanced Lymphoma

Keywords

Stimulator of interferon genes; STING agonist; Ovarian Neoplasms; Colorectal Neoplasms; Microsatellite stable colorectal; Microsatellite instable colorectal; Lymphoma; B-Cell Lymphomas; Solid Tumor; Advanced Tumor

Outcome Measures

Primary Outcomes (2)

• Incidence of dose limiting toxicities to determine the maximum tolerated dose (MTD) and Recommended Phase 2 dose of SNX281

  Percentage of participants with dose limiting toxicities associated with SNX281 alone or SNX281 combined with pembrolizumab (KEYTRUDA®) during the first cycle. Toxicity will be assessed using the NCI CTCAE Version 5.0

  Up to 28 Days

• Percentage of participants who experience adverse events and serious adverse events to determine safety and tolerability of SNX281 given as a single agent and in combination with pembrolizumab (KEYTRUDA®)

  Percentage of participants who experience adverse events and serious adverse events when given SNX281 as a single agent and in combination with pembrolizumab (KEYTRUDA®)

  Up to 20 weeks

Secondary Outcomes (7)

• Plasma concentration of SNX281 to characterize the pharmacokinetics (PK) parameters of SNX281 given as a single agent and in combination with pembrolizumab (KEYTRUDA®)

  Up to 20 weeks

• Plasma concentration of biomarker to determine pharmacodynamics (PD) response to SNX281 given as a single agent and in combination with pembrolizumab (KEYTRUDA®).

  Up to 20 weeks

• Objective response rate (ORR) to assess the clinical activity of SNX281 given as a single agent and in combination with pembrolizumab (KEYTRUDA®)

  Up to 40 months

• Duration of response (DoR) to assess the clinical activity of SNX281 given as a single agent and in combination with pembrolizumab (KEYTRUDA®)

  Up to 40 months

• Progression free survival (PFS) to assess the clinical activity of SNX281 given as a single agent and in combination with pembrolizumab (KEYTRUDA®)

  Up to 40 months

Study Arms (2)

SNX281 Monotherapy

EXPERIMENTAL

SNX281 will be administered weekly in Cycle 1 and then once every 3 weeks of each cycle thereafter for up to 6 cycles, or until disease progression or unacceptable toxicity occurs. Participants who are, in the opinion of the investigators, benefitting from treatment may be allowed to continue treatment with SNX281 beyond Cycle 6 with Sponsor approval. It is expected that up to approximately 66 participants will take part in this arm of the study. Subjects enrolled in the dose expansion phase of this arm may be eligible to add pembrolizumab (KEYTRUDA®) to their SNX281 therapy following identification of the maximum tolerated dose (MTD) or optimal dose of SNX281 in combination with pembrolizumab (KEYTRUDA®). Subjects must, in the opinion of the Investigator, have demonstrated tolerance to SNX281 and have experienced sub-optimal response to therapy (i.e., disease stability for 4 cycles or progression on treatment with SNX281 at any time).

Drug: SNX281

SNX281 in Combination with pembrolizumab (KEYTRUDA®)

EXPERIMENTAL

SNX281 will be administered in 3 of the 4 weeks in Cycle 1 and then once every 3 weeks of each cycle thereafter. Participants will also receive pembrolizumab (KEYTRUDA®) once every cycle for up to 6 cycles. The combination of SNX281 and pembrolizumab (KEYTRUDA®) will be given for up to 6 cycles, or until disease progression or unacceptable toxicity occurs. Participants who are, in the opinion of the investigators, benefitting from treatment may be allowed to continue treatment with SNX281 and pembrolizumab (KEYTRUDA®) (or SNX281 alone) beyond Cycle 6 with Sponsor approval. It is expected that up to approximately 68 participants will take part in this arm of the study.

Drug: SNX281; Drug: pembrolizumab

Interventions

SNX281 DRUG

SNX281 will be administered as an intravenous infusion on Days 1, 8, and 15 in Cycle 1 and on Day 1 of each subsequent cycle thereafter of each 21-day cycle for up to 6 cycles, or until disease progression or unacceptable toxicity occurs. Cycle 1 length varies from 21 days in monotherapy arm to 28 days in the combination arm.

SNX281 Monotherapy; SNX281 in Combination with pembrolizumab (KEYTRUDA®)

pembrolizumab DRUG

pembrolizumab (KEYTRUDA®) will be administered as an intravenous infusion on Day 8 in Cycle 1 (28-day cycle) and on Day 1 of each 21-day cycle thereafter for up to 6 cycles, or until disease progression or unacceptable toxicity occurs.

Also known as: KEYTRUDA®

SNX281 in Combination with pembrolizumab (KEYTRUDA®)

Eligibility Criteria

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

You may qualify if:

• Subjects must meet the following criteria in order to be included in the research study:
• Written informed consent, according to local guidelines, signed and dated by the subject or by a legal guardian prior to the performance of any study-specific procedures, sampling, or analyses
• At least 18 years-of-age at the time of signature of the informed consent form (ICF)
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
• Histological or cytological requirements as follows:
• a. Dose Escalation:
• i. All treatment arms: Subjects with histological or cytological documentation of advanced/recurrent solid tumors or lymphoma who have progressed on, are intolerant of, or are ineligible for existing standard therapies
• b. Dose Expansion:
• ii. SNX281 in Combination with pembrolizumab (KEYTRUDA®): Subjects with histological or cytological documentation of advanced/recurrent solid tumors or lymphoma who have relapsed on or are refractory to prior checkpoint inhibitor therapy given in an indicated setting. (Note: recruitment will be stopped in a given anatomical indication if no evidence of clinical response is observed in 15 subjects.)
• Measurable or evaluable disease according to disease-specific tumor assessment criteria. Subjects in dose expansion portions of the study must have at least 1 measurable lesion that has not been previously irradiated, or has progressed after prior irradiation.
• Subjects must have progressed on treatment with an anti-Programmed Cell Death Protein 1/Programmed Death-Ligand 1 (PD-1/L1) monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies. PD-1/L1 treatment progression is defined by meeting all of the following criteria:
• Has received at least 2 doses of an approved anti-PD-1/L1 mAb.
• Has demonstrated disease progression (PD) after PD-1/L1 as defined by RECIST v1.1. The initial evidence of PD is to be confirmed by a second assessment no less than four weeks from the date of the first documented PD, in the absence of rapid clinical progression.
• Progressive disease has been documented within 12 weeks from the last dose of anti-PD-1/L1 mAb.
• Progressive disease is determined according to iRECIST.

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from study entry:
• Malignancy other than the disease under study with the exception of those from which the subject has been disease-free for more than 2 years and not expected to affect the safety of the subject or the endpoints of the trial. Curatively treated non-melanoma skin cancer is permitted.
• Symptomatic central nervous system (CNS) metastases or asymptomatic CNS metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during the study screening), clinically stable and without the requirement of steroid treatment for at least 14 days prior to first dose of study treatment. Subjects with carcinomatous meningitis or leptomeningeal spread are excluded regardless of clinical stability.
• Active autoimmune disease that has required systemic disease modifying or immunosuppressive treatment within the last 2 years. Replacement therapy (e.g., thyroxine or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, insulin for type 1 diabetes, etc.) is permitted.
• Concurrent medical conditions requiring the use of systemic immunosuppressive treatment within 28 days before the first dose of study treatment. Physiologic doses of corticosteroids (not exceeding 10 mg/day prednisone or equivalent) for treatment of endocrinopathies or steroids with minimal systemic absorption, including topical, inhaled, or intranasal corticosteroids may be continued if the subject is on a stable dose.
• Current unstable liver or biliary disease per Investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Stable chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if subject otherwise meets entry criteria
• History of vasculitis at any time prior to study treatment
• Evidence or history of significant active bleeding or coagulation disorder that would compromise the subject's ability to adhere to the protocol.
• Has a known history of HIV infection. No HIV testing is required unless mandated by local health authority(ies).
• Has a known history of hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. No testing for hepatitis B or hepatitis C is required unless mandated by local health authority(ies).
• Has an active infection requiring systemic therapy.
• QT interval corrected for heart rate according to Fridericia's formula \>480 msec by machine read or human over-read. Pre-existing bundle branch block is permitted at the Investigator's discretion.
• Recent history (within the past 6 months) of acute diverticulitis, inflammatory bowel disease, intra-abdominal abscess, or gastrointestinal obstruction.
• Recent history (within 4 weeks of starting study) of allergen desensitization therapy
• History or evidence of cardiovascular risk including any of the following: recent (within the past 6 months) serious uncontrolled cardiac arrhythmia or clinically significant electrocardiogram (ECG) abnormalities including second degree (Type II) or third degree atrioventricular block; cardiomyopathy, myocardial infarction, acute coronary syndromes (including unstable angina pectoris), coronary angioplasty, stenting, or bypass grafting within the past 6 months before enrollment; congestive heart failure (Class II, III, or IV) as defined by the New York Heart Association functional classification system.

Sponsors & Collaborators

• Stingthera, Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (4)

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Thomas Jefferson University, Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania, 19107, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Bites and Stings; Ovarian Neoplasms; Colorectal Neoplasms; Lymphoma; Lymphoma, B-Cell

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Poisoning; Chemically-Induced Disorders; Wounds and Injuries; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin

Study Officials

• Melissa Johnson, MD

  SCRI Development Innovations, LLC

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: October 23, 2020
• First Posted: October 30, 2020
• Study Start: November 18, 2020
• Primary Completion: January 6, 2024
• Study Completion: January 6, 2024
• Last Updated: January 30, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)