Phase I/II Trial Investigating the Safety, Tolerability, Pharmacokinetics, Immune and Clinical Activity of SX-682 in Combination With BinTrafusp Alfa (M7824 or TGF-beta "Trap"/PD-L1) With CV301 TRICOM in Advanced Solid Tumors (STAT)
2 other identifiers
interventional
12
1 country
1
Brief Summary
Background: Combination immunotherapy techniques are being explored to improve responses and enhance benefits in people with cancer. Researchers want to see if this type of treatment can help people with advanced solid tumors. Objective: To find a safe dose of SX-682 in combined treatment with Bintrafusp alfa and BN-CV301 vaccines and to see if this treatment will cause tumors to shrink. Eligibility: Adults age 18 and older with metastatic cancer may be eligible for the first part of the trial. Adults age 18 and older with metastatic triple negative breast cancer or p16 negative head and neck squamous cell cancer, and who are not candidates for curative surgery may be eligible for the second part of the trial. Design: Participants will be screened under a separate protocol. Participants may have tumor biopsies. They will have physical exams. Their symptoms and medicines will be reviewed. They will have blood tests. They will have electrocardiograms to evaluate their heart. Participants will have imaging scans of the chest, abdomen, and pelvis. They may have a procedure where a small tube with a tiny video camera is put into the nose to look at the throat if they have head and neck cancers. Participants will get bintrafusp alfa through an intravenous catheter. For this, a small tube is put into an arm vein. They will get BN-CV301 vaccines as injections in the arm or thigh. They will take SX-682 by mouth twice a day. They will take the study drugs up to 2 years. They will keep a medicine diary. Participants will have study visits every 2 weeks. They will have 1 or 2 follow-up visits within 30 days after they stop treatment. Then they will be monitored by phone or email for 2 years.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Nov 2020
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 2, 2020
CompletedFirst Posted
Study publicly available on registry
October 5, 2020
CompletedStudy Start
First participant enrolled
November 24, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 7, 2023
CompletedResults Posted
Study results publicly available
May 3, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
May 19, 2023
CompletedFebruary 3, 2025
January 1, 2025
2.2 years
October 2, 2020
August 30, 2022
January 24, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
Dose Limiting Toxicities (DLT)
A DLT is defined as any one of the following adverse events (AEs), as defined by Common Terminology Criteria for Adverse Events (CTCAE v5.0), that is possibly attributable to study drugs by the Investigator, that occur within 28 days after the start of study therapy: Any Grade 4 (life threatening) AEs, except for example, laboratory values that are determined to not be clinically significant or single laboratory valued that resolve to Grade ≤ 1 or baseline grade within 7 days with adequate medical management. Average corrected QT interval by Fridericia (QTcF)≥ 501 msec or \> 60 msec change from baseline (Grade 3). Any Grade 3 (severe) AEs except for example, Grade 3 flu-like symptoms or fever, as well as associated symptoms of fatigue, headaches, nausea, emesis which can be controlled with conservative medical management. Any grade 3 or higher adverse event or unexpected toxicities due to the combination of therapies that would not be expected with individual agents alone.
DLT observation period (first 4 weeks)
Number of Participants With Grades 3-5 Adverse Events (AEs) Related and/or Unrelated to SX-682 + BinTrafusp Alfa (M7824) + BN-CV301
Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to AE.
Approximately 16 months and 11 days
Maximum Tolerated Dose (MTD) of SX-682 Followed by BinTrafusp Alfa (M7824) and CV301 Vaccines in Participants With Advanced or Metastatic Solid Tumors.
The MTD is the dose at which no more than 1 of 6 subjects taking SX-682 followed by M7824 and CV301 vaccines experience a dose-limiting toxicity (DLT). A DLT is defined as any one of the following adverse events (AEs), as defined by Common Terminology Criteria for Adverse Events (CTCAE v5.0), that is possibly attributable to study drugs by the Investigator, that occur within 28 days after the start of study therapy.
Period of Safety lead-in (monotherapy), approximately 28 days
Recommended Phase II Dose (RP2D) of SX-682 With BinTrafusp Alfa (M7824) and CV301 Vaccines in Participants With Advanced or Metastatic Solid Tumors.
Recommended phase II dose is defined as the dose defined in the phase I portion of a study that will be administered to participants on the phase II portion.
Approximately 28 days
Percentage of Participants Who Experience a Response
The percentage of participants who experience a response will be reported along with 95% two-sided confidence intervals. The objective response is the best overall response recorded from the start of treatment until disease progression/recurrence per the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Stable Disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
11 months
Secondary Outcomes (4)
Percentage of Participants Disease Control Rate (DCR): Complete Response (CR)+ Partial Response (PR) + Stable Disease (SD)
Date first participant enrolled and ending on the off treatment date of the last participant on treatment (i.e., assessed beyond the primary completion date), approximately 15 months and 14 days.
Progression-free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors (RECIST)1.1.
Time from start of treatment to time of progression or death, whichever occurs first, approximately 10 months
Pharmacokinetic Profile of SX-682 as a Single Agent and in Combination
Predose, 30 minutes, 60 minutes, 120 minutes, <6 hours of 2nd dose, and end of infusion (EOI)
Pharmacodynamic Profile of SX-682 as a Single Agent and in Combination
Predose, 30 minutes, 60 minutes, 120 minutes, <6 hours of 2nd dose, and end of infusion (EOI)
Other Outcomes (1)
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
Date treatment consent signed to date off study, approximately 5 months and 9 days, 13 months and 17 days, and 6 months and 1 day for DL1, DL2, and DL3 respectively. Adverse events were assessed beyond the primary completion date.
Study Arms (3)
Phase I Dose Level 1(DL1) 25mg SX-682 monotherapy sequentially foll/by 1200mg BinTraFusp Alfa +CV301
EXPERIMENTALParticipants with any solid tumor will receive a 2- week monotherapy lead-in of SX-682 DL2 50 mg by mouth (PO) twice a day (BID) followed sequentially by treatment with a dual combination of + BinTrafusp Alfa (M7824) 1200 mg fixed dose intravenous (IV) + BN-CV301. Participants will be evaluated for dose-limiting toxicities at the completion of the dose level before enrollment to the next dose level begins
Phase I Dose Level 2 (DL2) 50 mg SX-682 sequentially followed by 1200mg BinTraFusp Alfa + CV301
EXPERIMENTALParticipants with any solid tumor will receive a 2- week monotherapy lead-in of SX-682 DL2 50 mg by mouth (PO) twice a day (BID) followed sequentially by treatment with a dual combination of + BinTrafusp Alfa (M7824) 1200 mg fixed dose intravenous (IV) + BN-CV301. Participants will be evaluated for dose-limiting toxicities at the completion of the dose level before enrollment to the next dose level begins
Phase I Dose Level 3 (DL3) 100 mg SX-682 sequentially followed by 1200mg BinTraFusp Alfa +CV301
EXPERIMENTALParticipants with any solid tumor will receive a 2- week monotherapy lead-in of SX-682 DL1 100 mg by mouth (PO) twice a day (BID) followed sequentially by treatment with a dual combination of + BinTrafusp Alfa (M7824) 1200 mg fixed dose intravenous (IV) + BN-CV301. Participants will be evaluated for dose-limiting toxicities at the completion of the dose level before enrolling onto the next dose level.
Interventions
SX-682 will be given orally at designated dose twice a day every day
Subjects will receive M7824 at a flat dose of 1,200 mg intravenously on Days 1 and 15 of each cycle.
MVA-BN-CV301 will be given as four subcutaneous injections (4x10\^8 Inf.U/0.5ml twice during Cycle 1 (Days 1 and 15)
FPV-CV301 will be given as one subcutaneous injection (1x10\^9 Inf.U/0.5ml) on Day 1 starting at cycle 2 through cycle 5 (every 4 weeks) then on Day 1 of every 3 cycles (Cycles 8 and Cycle 11).
Eligibility Criteria
You may qualify if:
- Participants must have histologically or cytologically confirmed:
- Metastatic or locally advanced, Solid tumor (Cohort 1)
- Metastatic or locally recurrent, non-resectable Triple Negative Breast Cancer (TNBC), defined as estrogen receptor (ER) \< 10%, progesterone receptor (PR) \< 10% per immunohistochemistry (IHC) and human epidermal growth factor receptor 2 (HER2) negative. HER2 negative or unamplified breast cancer is defined as IHC 0 or 1+ or IHC 2+ with FISH average HER2 copy number \< 4.0 signals per cell or HER2/chromosome 17 (CEP17) \< 2.0 with average HER2 copy number \< 4.0 signals per cell.\[89\] HER2 testing must have been performed in a laboratory accredited by the College of American Pathology (CAP) or another accrediting entity (Cohort 2).
- Metastatic or locally recurrent, non-resectable p16 negative Head and Neck Squamous Cell Cancer (HNSCC). Oropharyngeal tumors must be negative for p16 overexpression by IHC per American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines and in a CAP accredited lab.\[90\] All other head and neck malignancies do not require p16 testing (Cohort 3).
- Participants must have histologically or cytologically confirmed metastatic or locally advanced disease. Historical reports from a CAP accredited lab are acceptable.
- Subjects in Arms 1 and 2 may have disease that is measurable or non-measurable but evaluable disease (e.g. present on bone scan, rising tumor markers, non-measurable by Response Evaluation Criteria in Solid Tumors (RECIST) but visible on computed tomography (CT) scan). Participants with third space fluid (for example pleural effusions) as only site of disease will not be eligible. Subjects in Arm 3 must have measurable disease according to RECIST 1.1
- Participants must
- have received at least one prior systemic therapy for metastatic or locally advanced disease, unless there is no standard treatment available,
- not tolerate standard first line treatment,
- decline standard treatment after appropriate counseling has been provided.
- Note: Participants in Arm 3, Cohort 3 who have programmed death-ligand 1 (PD-L1) positive triple-negative breast cancer (TNBC) must have progressed on atezolizumab + nab-paclitaxel. Participants in Arm 3, Cohort 3 (p16 negative head and neck squamous cell carcinomas (HNSCC) must have progressed on or been intolerant to a regimen involving a platinum drug or cetuximab monotherapy.
- Age greater than or equal to 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- Participants must have adequate organ and marrow function as defined below:
- Absolute neutrophil count (ANC) \>1,500/mcL
- +18 more criteria
You may not qualify if:
- Participants who are receiving any other investigational agents.
- Participants with active brain metastases or central nervous system metastasis (less than 28 days out from definitive radiotherapy or surgery of brain metastasis) are excluded from this clinical trial. However, patients with treated brain metastasis are eligible if there is no magnetic resonance imaging (MRI) evidence of progression for 6 weeks after treatment is complete and the MRI within 28 days prior to enrollment. Participants requiring immunosuppressive doses of systemic corticosteroids (\> 10 mg/day prednisone equivalent) for palliation are excluded. Patients with evidence of intratumoral or peritumoral brain metastasis hemorrhage on screening imaging are also excluded unless the hemorrhage of brain metastases is grade \< 1 and has been stable on two consecutive imaging scans.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to any of study drugs
- Steroid use or active autoimmune disease that might deteriorate when receiving an immunostimulatory agent with the exception of:
- Diabetes type I, eczema, vitiligo, alopecia, psoriasis, hypo- or hyperthyroid disease or other mild autoimmune disorder not requiring immunosuppressive treatment;
- Participants requiring hormone replacement with corticosteroid are eligible if the steroids are administered only for the purpose of adrenal insufficiency and at doses of \<10 mg of prednisone or equivalent per day;
- Administration of steroids for other conditions through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) is acceptable;
- Participants on physiologic doses of systemic intravenous or oral corticosteroid therapy (greater than or equal to the equivalent of prednisone 10 mg/day.
- The use of corticosteroids as premedication for contrast-enhanced studies which is allowed prior to enrollment.
- Participants with a history of serious intercurrent chronic or acute illness, such as cardiac or pulmonary disease, hepatic disease, bleeding diathesis or recent (within 3 months) clinically significant bleeding events or other illness considered by the Investigator as high risk for investigational drug treatment.
- History of second malignancy within 3 years of enrollment except for the following: adequately treated localized skin cancer, ductal carcinoma in situ, cervical carcinoma in situ, superficial bladder cancer or other localized malignancy which has been adequately treated.
- Receipt of any organ transplantation requiring ongoing immunosuppression including allogenic stem-cell transplant.
- Participants with bone metastases who have initiated denosumab or a bisphosphonate therapy within 28 days prior to enrollment. Continuation of prior therapy is allowed.
- Participants who have a corrected QT interval by Fridericia (QTcf) interval \> 475 msec or \> 480 msec with a bundle branch block (BBB) on screening electrocardiogram.
- Participants with a personal or family history of long-QT syndrome or are on a concomitant drug that is known to cause significant QTc prolongation within 2 weeks or 5 half-lives (whichever is shorter) of enrollment
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. James Gulley
- Organization
- National Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
James L Gulley, M.D.
National Cancer Institute (NCI)
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Investigator
Study Record Dates
First Submitted
October 2, 2020
First Posted
October 5, 2020
Study Start
November 24, 2020
Primary Completion
February 7, 2023
Study Completion
May 19, 2023
Last Updated
February 3, 2025
Results First Posted
May 3, 2023
Record last verified: 2025-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
- Access Criteria
- Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.
All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to database of Genotypes and Phenotypes (dbGaP).