Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT04609579
Other study ID # SNX281-001
Secondary ID MK-3475-D44KEYNO
Status Terminated
Phase Phase 1
First received
Last updated
Start date November 18, 2020
Est. completion date January 6, 2024

Study information

Verified date January 2024
Source Stingthera, Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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®)


Description:

SNX281 is a small molecule activator of the Stimulator of Interferon Genes (STING) protein, with good drug-like properties. Activation of STING initiates the innate immune response and enhances the adaptive immune response, which could potentially activate immune responses to tumors and enhance the response to certain immunotherapies. This study is a phase I, first in human, open-label study of SNX281 conducted in subjects with advanced solid tumors and lymphomas. The study will comprise of two treatment arms: one evaluating SNX281 as a single-agent, and the other evaluating SNX281 in combination with pembrolizumab (KEYTRUDA®). Each treatment arm is designed to include a dose escalation phase followed by a dose expansion phase intended to establish the recommended Phase 2 dose (RP2D). In the dose escalation phase of each treatment arm, successive cohorts of participants will receive increasing doses of SNX281 designed to determine the maximum tolerated dose (MTD), the dose with maximum pharmacologic activity, or the maximum feasible dose, as a single-agent and in combination with pembrolizumab (KEYTRUDA®). The dose expansion phases of each treatment arm will begin following the determination of an MTD or alternative dose of SNX281 in each respective treatment arm. The single-agent treatment arm of SNX281 is planned to evaluate at least 2 expansion cohorts in ovarian cancer and colorectal carcinoma while the combination treatment arm of SNX281 and pembrolizumab (KEYTRUDA®) is planned to enroll subjects with advanced cancer who have relapsed on or have become refractory to prior immune checkpoint therapy given in an indicated setting.


Read more »

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
SNX281
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.
pembrolizumab
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.

Locations

Country Name City State
United States Sarah Cannon Research Institute at HealthONE Denver Colorado
United States Tennessee Oncology Nashville Tennessee
United States Thomas Jefferson University, Sidney Kimmel Cancer Center Philadelphia Pennsylvania
United States Florida Cancer Specialists Sarasota Florida

Sponsors (2)

Lead Sponsor Collaborator
Stingthera, Inc. Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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
Primary 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 Plasma concentration of SNX281 to characterize the pharmacokinetics (PK) parameters of SNX281 given as a single agent and in combination with pembrolizumab (KEYTRUDA®) Plasma concentration of SNX281 from all participants given as a single agent and in combination with pembrolizumab (KEYTRUDA®). Up to 20 weeks
Secondary Plasma concentration of biomarker to determine pharmacodynamics (PD) response to SNX281 given as a single agent and in combination with pembrolizumab (KEYTRUDA®). Plasma concentration of biomarker from all participants receiving SNX281 as a single agent and in combination with pembrolizumab (KEYTRUDA®). Up to 20 weeks
Secondary Objective response rate (ORR) to assess the clinical activity of SNX281 given as a single agent and in combination with pembrolizumab (KEYTRUDA®) Proportion of participants with confirmed complete response (CR) or partial response (PR) according to disease specific response criteria
RECIST 1.1/iRECIST:
A CR is the complete disappearance of all target and non-target lesions. A PR is a =30% decrease in the sum of diameters of target lesions from the baseline sum
RECIL2017:
A CR is the complete disappearance of all non-target/target lesions/all nodes with long axis <10 mm, or =30% decrease in the sum of longest diameters of target lesions (PR) with normalization of FDG-PET and no bone marrow involvement or appearance of new lesion. A PR is =30% decrease in the sum of longest diameters of target lesions, with positive FDG-PET with any bone marrow involvement and no appearance of new lesions and no progression of non-target lesions.
Up to 40 months
Secondary Duration of response (DoR) to assess the clinical activity of SNX281 given as a single agent and in combination with pembrolizumab (KEYTRUDA®) Defined as: Time from first documented response (CR or PR) to first evidence of progressive disease (PD) per RECIST 1.1 and RECIL 2017 or confirmed PD (iCPD) per iRECIST or death due to any cause.
RECIST 1.1- PD: =20% increase in target lesions and =5mm from smallest sum, any new lesions, or unequivocal progression of non-target lesions.
iRECIST- iCPD: Confirmation of further increase in tumor burden, compared to the last assessment where RECIST 1.1 definition of progression had been met, as evidenced by- =5 mm increase in progressed target lesion sum, increased size of previous unequivocally progressed non-target lesions, =5 mm increase in sum of previously identified new lesions, or new progression in target or non-target lesions or additional new lesions not previously identified.
RECIL 2017- PD: New lesion appearance or =20% increase in sum of target lesions. If lymph N<15 mm post therapy,a =5 mm increase with longest diameter exceeds 15mm
Up to 40 months
Secondary Progression free survival (PFS) to assess the clinical activity of SNX281 given as a single agent and in combination with pembrolizumab (KEYTRUDA®) PFS: Time from the first day of study drug administration to disease progression (PD) as defined by disease-specific response criteria (RECIST 1.1, iRECIST, or RECIL2017), or death on study.
RECIST 1.1- PD: =20% increase in target lesions sum and =5mm from smallest sum, any new lesions, or unequivocal progression of non-target lesions.
iRECIST- iCPD: Confirmation of further increase in tumor burden, compared to the last assessment where RECIST 1.1 definition of progression had been met, as evidenced by- =5 mm increase in progressed target lesion sum, increased size of previous unequivocally progressed non-target lesions, =5 mm increase in sum of previously identified new lesions, or new progression in target or non-target lesions or additional new lesions not previously identified.
RECIL 2017- PD: New lesion appearance or =20% increase in sum of longest diameters of target lesions. For lymph nodes measuring <15 mm post therapy, a =5 mm increase with longest diameter exceeds 15mm.
Up to 40 months
Secondary Overall survival (OS) to assess the clinical activity of SNX281 given as a single agent and in combination with pembrolizumab (KEYTRUDA®) Overall survival (OS) is defined as the time from the first day of study drug administration (Day 1) to death Up to 40 months
Secondary Disease control rate (DCR) to assess the clinical activity of SNX281 given as a single agent and in combination with pembrolizumab (KEYTRUDA®) DCR is: Proportion of subjects who achieved either a complete response (CR), partial response (PR), or stable disease (SD) at their first scheduled disease assessment according to disease-specific response criteria.
RECIST 1.1/iRECIST CR: disappearance of all target/non-target lesions. PR: =30% decrease in the sum of diameters of target lesions from baseline sum. SD: Neither sufficient shrinkage to qualify for a PR nor sufficient increase in lesions for a PD
RECIL2017 CR: Disappearance of all target/nodal lesions or =30% decrease in the sum of longest diameters of target lesions with normal FDG-PET and no bone marrow (BM) involvement or new lesion.
PR: =30% decrease in the sum of longest diameters of target lesions with positive FDG-PET with any BM involvement and no new lesion.
SD: Less than 10% decrease or up to 20% increase in the sum of longest diameter of target lesions with any FDG-PET result or any bone marrow involvement and no appearance of new lesion
Up to 40 months
See also
  Status Clinical Trial Phase
Recruiting NCT06223308 - A Study Evaluating the Safety and Efficacy of HB0028 in Subjects With Advanced Solid Tumors Phase 1/Phase 2
Not yet recruiting NCT05515185 - B7-H3 Targeting CAR-T Cells Therapy for B7-H3 Positive Solid Tumors Early Phase 1
Completed NCT05508100 - Dose Confirmation and Dose Expansion Phase 1 Study of IO-108 and IO-108 + Anti-PD-1 in Solid Tumors Phase 1
Recruiting NCT05094804 - A Study of OR2805, a Monoclonal Antibody Targeting CD163, Alone and in Combination With Anticancer Agents Phase 1/Phase 2
Completed NCT02836600 - A Study of LY3039478 in Japanese Participants With Advanced Solid Tumors Phase 1
Recruiting NCT04890613 - Study of CX-5461 in Patients With Solid Tumours and BRCA1/2, PALB2 or Homologous Recombination Deficiency (HRD) Mutation Phase 1
Recruiting NCT04390737 - Evaluate the Safety and Clinical Activity of HH2853 Phase 1/Phase 2
Recruiting NCT06007482 - A Study of ES009 in Subjects With Locally Advanced or Metastatic Solid Tumors Phase 1
Recruiting NCT05981703 - A Study Investigating BGB-26808 Alone or in Combination With Tislelizumab in Participants With Advanced Solid Tumors Phase 1
Completed NCT04108676 - Effect of Omeprazole on PK of Fluzoparib in Healthy Male Subjects Phase 1
Recruiting NCT05798611 - Study of ART0380 in Patients With Biologically Selected Solid Tumors Phase 2
Recruiting NCT05076396 - PM14 Administered Intravenously to Patients With Advanced Solid Tumors Phase 1
Recruiting NCT06054932 - Safety, Tolerability, and Immunogenicity of LK101 Alone in Participants With Incurable Solid Tumors Phase 1
Recruiting NCT06008366 - A Phase 1/2 Study of 7MW3711 in Advanced Solid Tumors Phase 1/Phase 2
Recruiting NCT04825392 - A Phase Ib Study of HX008 in Patients With Advanced Solid Tumors Phase 1
Active, not recruiting NCT04242199 - Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099280 in Participants With Advanced Solid Tumors Phase 1
Not yet recruiting NCT06365918 - Study of VG2025 Delivered Intraperitoneally in Patients With Advanced Solid Tumors With Carcinomatosis Phase 1
Recruiting NCT05461287 - Safety, Tolerability and Pharmacokinetics Study of QLS31904 in Patients With Advanced Solid Tumors Phase 1
Recruiting NCT05443126 - A Study of EP0031 in Patients With Advanced RET-altered Malignancies Phase 1/Phase 2
Recruiting NCT05569057 - A Phase I Trial of SIM1811-03 in Subjects With Advanced Solid Tumors and Cutaneous T-cell Lymphoma Phase 1