Last reviewed · How we verify

NCT04574583

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)

Completed Phase 1, PHASE2 Results posted Last updated 3 February 2025
What this trial tests

Phase 1, PHASE2 trial testing SX-682 in Metastatic Cancer in 12 participants. Completed in 19 May 2023.

Timeline
24 November 2020
Primary endpoint
7 February 2023
19 May 2023

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment12
Start date24 November 2020
Primary completion7 February 2023
Estimated completion19 May 2023
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Metastatic Cancer or Solid Tumors. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Dose Limiting Toxicities (DLT) Primary · DLT observation period (first 4 weeks)

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 fro

GroupValue95% CI
Phase I Dose Level 1(DL1) 25mg SX-682 Monotherapy Sequentially Foll/by 1200mg BinTraFusp Alfa +CV3010
Phase I Dose Level 2 (DL2) 50 mg SX-682 Sequentially Followed by 1200mg BinTraFusp Alfa + CV3011
Phase I Dose Level 3 (DL3) 100 mg SX-682 Sequentially Followed by 1200mg BinTraFusp Alfa +CV3010
Number of Participants With Grades 3-5 Adverse Events (AEs) Related and/or Unrelated to SX-682 + BinTrafusp Alfa (M7824) + BN-CV301 Primary · Approximately 16 months and 11 days

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.

Grade 3 Related
GroupValue95% CI
Phase I Dose Level 1(DL1) 25mg SX-682 Monotherapy Sequentially Foll/by 1200mg BinTraFusp Alfa +CV3012
Phase I Dose Level 2 (DL2) 50 mg SX-682 Sequentially Followed by 1200mg BinTraFusp Alfa + CV3012
Phase I Dose Level 3 (DL3) 100 mg SX-682 Sequentially Followed by 1200mg BinTraFusp Alfa +CV3012
Grade 4 Related
GroupValue95% CI
Phase I Dose Level 1(DL1) 25mg SX-682 Monotherapy Sequentially Foll/by 1200mg BinTraFusp Alfa +CV3010
Phase I Dose Level 2 (DL2) 50 mg SX-682 Sequentially Followed by 1200mg BinTraFusp Alfa + CV3010
Phase I Dose Level 3 (DL3) 100 mg SX-682 Sequentially Followed by 1200mg BinTraFusp Alfa +CV3010
Grade 5 Related
GroupValue95% CI
Phase I Dose Level 1(DL1) 25mg SX-682 Monotherapy Sequentially Foll/by 1200mg BinTraFusp Alfa +CV3010
Phase I Dose Level 2 (DL2) 50 mg SX-682 Sequentially Followed by 1200mg BinTraFusp Alfa + CV3010
Phase I Dose Level 3 (DL3) 100 mg SX-682 Sequentially Followed by 1200mg BinTraFusp Alfa +CV3010
Grade 3 Unrelated
GroupValue95% CI
Phase I Dose Level 1(DL1) 25mg SX-682 Monotherapy Sequentially Foll/by 1200mg BinTraFusp Alfa +CV3011
Phase I Dose Level 2 (DL2) 50 mg SX-682 Sequentially Followed by 1200mg BinTraFusp Alfa + CV3014
Phase I Dose Level 3 (DL3) 100 mg SX-682 Sequentially Followed by 1200mg BinTraFusp Alfa +CV3012
Grade 4 Unrelated
GroupValue95% CI
Phase I Dose Level 1(DL1) 25mg SX-682 Monotherapy Sequentially Foll/by 1200mg BinTraFusp Alfa +CV3010
Phase I Dose Level 2 (DL2) 50 mg SX-682 Sequentially Followed by 1200mg BinTraFusp Alfa + CV3010
Phase I Dose Level 3 (DL3) 100 mg SX-682 Sequentially Followed by 1200mg BinTraFusp Alfa +CV3010
Grade 5 Unrelated
GroupValue95% CI
Phase I Dose Level 1(DL1) 25mg SX-682 Monotherapy Sequentially Foll/by 1200mg BinTraFusp Alfa +CV3010
Phase I Dose Level 2 (DL2) 50 mg SX-682 Sequentially Followed by 1200mg BinTraFusp Alfa + CV3011
Phase I Dose Level 3 (DL3) 100 mg SX-682 Sequentially Followed by 1200mg BinTraFusp Alfa +CV3010
Maximum Tolerated Dose (MTD) of SX-682 Followed by BinTrafusp Alfa (M7824) and CV301 Vaccines in Participants With Advanced or Metastatic Solid Tumors. Primary · Period of Safety lead-in (monotherapy), approximately 28 days

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.

GroupValue95% CI
All ParticipantsNA
Recommended Phase II Dose (RP2D) of SX-682 With BinTrafusp Alfa (M7824) and CV301 Vaccines in Participants With Advanced or Metastatic Solid Tumors. Primary · Approximately 28 days

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.

GroupValue95% CI
All ParticipantsNA
Percentage of Participants Who Experience a Response Primary · 11 months

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 su

Complete Response
GroupValue95% CI
Phase I Solid Tumor Dose Level 1 (DL1) Sequential Dose Escalation0
Phase I Solid Tumor Dose Level 2 (DL2) Combination Dose Escalation0
Phase I Solid Tumor Dose Level 3 (DL3) Disease-Specific Expansion0
Partial Response
GroupValue95% CI
Phase I Solid Tumor Dose Level 1 (DL1) Sequential Dose Escalation0
Phase I Solid Tumor Dose Level 2 (DL2) Combination Dose Escalation0
Phase I Solid Tumor Dose Level 3 (DL3) Disease-Specific Expansion0
Stable Disease
GroupValue95% CI
Phase I Solid Tumor Dose Level 1 (DL1) Sequential Dose Escalation100
Phase I Solid Tumor Dose Level 2 (DL2) Combination Dose Escalation60
Phase I Solid Tumor Dose Level 3 (DL3) Disease-Specific Expansion0
Progressive Disease
GroupValue95% CI
Phase I Solid Tumor Dose Level 1 (DL1) Sequential Dose Escalation100
Phase I Solid Tumor Dose Level 2 (DL2) Combination Dose Escalation40
Phase I Solid Tumor Dose Level 3 (DL3) Disease-Specific Expansion100
Percentage of Participants Disease Control Rate (DCR): Complete Response (CR)+ Partial Response (PR) + Stable Disease (SD) Secondary · 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.

The percentage of participants disease control rate (DCR): Complete response (CR)+ partial response (PR) + stable disease (SD) was measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response is disappearance of all target lesions and 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

Complete Response
GroupValue95% CI
Phase I Dose Level 1(DL1) 25mg SX-682 Monotherapy Sequentially Foll/by 1200mg BinTraFusp Alfa +CV3010
Phase I Dose Level 2 (DL2) 50 mg SX-682 Sequentially Followed by 1200mg BinTraFusp Alfa + CV3010
Phase I Dose Level 3 (DL3) 100 mg SX-682 Sequentially Followed by 1200mg BinTraFusp Alfa +CV3010
Partial Response
GroupValue95% CI
Phase I Dose Level 1(DL1) 25mg SX-682 Monotherapy Sequentially Foll/by 1200mg BinTraFusp Alfa +CV3010
Phase I Dose Level 2 (DL2) 50 mg SX-682 Sequentially Followed by 1200mg BinTraFusp Alfa + CV3010
Phase I Dose Level 3 (DL3) 100 mg SX-682 Sequentially Followed by 1200mg BinTraFusp Alfa +CV3010
Stable Disease
GroupValue95% CI
Phase I Dose Level 1(DL1) 25mg SX-682 Monotherapy Sequentially Foll/by 1200mg BinTraFusp Alfa +CV301100
Phase I Dose Level 2 (DL2) 50 mg SX-682 Sequentially Followed by 1200mg BinTraFusp Alfa + CV30160
Phase I Dose Level 3 (DL3) 100 mg SX-682 Sequentially Followed by 1200mg BinTraFusp Alfa +CV3010
Progression-free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors (RECIST)1.1. Secondary · Time from start of treatment to time of progression or death, whichever occurs first, approximately 10 months

PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progression per the RECIST is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progressions.

GroupValue95% CI
Phase I Dose Level 1(DL1) 25mg SX-682 Monotherapy Sequentially Foll/by 1200mg BinTraFusp Alfa +CV3012.01.5 – 6.9
Phase I Dose Level 2 (DL2) 50 mg SX-682 Sequentially Followed by 1200mg BinTraFusp Alfa + CV3013.41.0 – 10.4
Phase I Dose Level 3 (DL3) 100 mg SX-682 Sequentially Followed by 1200mg BinTraFusp Alfa +CV3011.81.3 – 2.3
Pharmacokinetic Profile of SX-682 as a Single Agent and in Combination Secondary · Predose, 30 minutes, 60 minutes, 120 minutes, <6 hours of 2nd dose, and end of infusion (EOI)

Plasma and serum samples will be drawn and may be analyzed by a validated immunoassay to quantitate SX-682 as a single agent and in combination or by a validated electrochemiluminescence immunoassay to detect the presence of M7824 concentration.

Participant 1 - PRE, Day 14
GroupValue95% CI
Phase I Dose Level 1(DL1) 25mg SX-682 Monotherapy Sequentially Foll/by 1200mg BinTraFusp Alfa +CV301NA
Participant 1 - 30 minutes, Day 14
GroupValue95% CI
Phase I Dose Level 1(DL1) 25mg SX-682 Monotherapy Sequentially Foll/by 1200mg BinTraFusp Alfa +CV3017.88
Participant 1 - 60 minutes, Day 14
GroupValue95% CI
Phase I Dose Level 1(DL1) 25mg SX-682 Monotherapy Sequentially Foll/by 1200mg BinTraFusp Alfa +CV30117.7
Participant 1 - 120 minutes, Day 14
GroupValue95% CI
Phase I Dose Level 1(DL1) 25mg SX-682 Monotherapy Sequentially Foll/by 1200mg BinTraFusp Alfa +CV301104
Participant 1 - 180 minutes, Day 14
GroupValue95% CI
Phase I Dose Level 1(DL1) 25mg SX-682 Monotherapy Sequentially Foll/by 1200mg BinTraFusp Alfa +CV301124
Participant 1 - <6 hours (HR) of 2nd dose, Day 14
GroupValue95% CI
Phase I Dose Level 1(DL1) 25mg SX-682 Monotherapy Sequentially Foll/by 1200mg BinTraFusp Alfa +CV301105
Participant 1 - PRE, Day 7
GroupValue95% CI
Phase I Dose Level 1(DL1) 25mg SX-682 Monotherapy Sequentially Foll/by 1200mg BinTraFusp Alfa +CV301214
Participant 1 - 30 minutes, Day 7
GroupValue95% CI
Phase I Dose Level 1(DL1) 25mg SX-682 Monotherapy Sequentially Foll/by 1200mg BinTraFusp Alfa +CV301193
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) Secondary · 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.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent

GroupValue95% CI
Phase I Dose Level 1(DL1) 25mg SX-682 Monotherapy Sequentially Foll/by 1200mg BinTraFusp Alfa +CV3013
Phase I Dose Level 2 (DL2) 50 mg SX-682 Sequentially Followed by 1200mg BinTraFusp Alfa + CV3016
Phase I Dose Level 3 (DL3) 100 mg SX-682 Sequentially Followed by 1200mg BinTraFusp Alfa +CV3013

Adverse events — posted to ClinicalTrials.gov

Time frame: 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.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase I Dose Level 1(DL1) 25mg SX-682 Monotherapy Sequentially Foll/by 1200mg BinTraFusp Alfa +CV301
Serious: 1/3 (33%)
Deaths: 1/3
Phase I Dose Level 2 (DL2) 50 mg SX-682 Sequentially Followed by 1200mg BinTraFusp Alfa + CV301
Serious: 3/6 (50%)
Deaths: 3/6
Phase I Dose Level 3 (DL3) 100 mg SX-682 Sequentially Followed by 1200mg BinTraFusp Alfa +CV301
Serious: 1/3 (33%)
Deaths: 2/3

Serious adverse events (9 terms)

ReactionSystemPhase I Dose Level 1(DL1) …Phase I Dose Level 2 (DL2)…Phase I Dose Level 3 (DL3)…
AnemiaBlood and lymphatic system disorders
Disease progressionGeneral disorders
Esophageal hemorrhageGastrointestinal disorders
HematuriaRenal and urinary disorders
Hepatobiliary disorders - Other, hepatobiliary dilatationHepatobiliary disorders
Respiratory, thoracic and mediastinal disorders - Other, COVID-19 infectionRespiratory, thoracic and mediastinal disorders
StrokeNervous system disorders
Upper gastrointestinal hemorrhageGastrointestinal disorders
Urinary tract infectionInfections and infestations
Other adverse events (67 terms — click to expand)

ReactionSystemPhase I Dose Level 1(DL1) …Phase I Dose Level 2 (DL2)…Phase I Dose Level 3 (DL3)…
Injection site reactionGeneral disorders
FatigueGeneral disorders
AnemiaBlood and lymphatic system disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
ConstipationGastrointestinal disorders
DizzinessNervous system disorders
Dry skinSkin and subcutaneous tissue disorders
Flu like symptomsGeneral disorders
HeadacheNervous system disorders
HyperthyroidismEndocrine disorders
Lipase increasedInvestigations
Neutrophil count decreasedInvestigations
Oral hemorrhageGastrointestinal disorders
White blood cell decreasedInvestigations
Abdominal painGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Alkaline phosphatase increasedInvestigations
Anal hemorrhageGastrointestinal disorders
AnorexiaMetabolism and nutrition disorders
Aspartate aminotransferase increasedInvestigations
Back painMusculoskeletal and connective tissue disorders
Blood bilirubin increasedInvestigations
Bone painMusculoskeletal and connective tissue disorders
Dry mouthGastrointestinal disorders
DysphasiaNervous system disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Edema limbsGeneral disorders
Enterocolitis infectiousInfections and infestations
FeverGeneral disorders
Gastric hemorrhageGastrointestinal disorders
General disorders and administration site conditions - Other, Mucosal bleeding-hematuriaGeneral disorders
General disorders and administration site conditions - Other, specifyGeneral disorders
General disorders and administration site conditions - Other, specifyGeneral disorders
HematuriaRenal and urinary disorders
Hemorrhoidal hemorrhageGastrointestinal disorders
HypoalbuminemiaMetabolism and nutrition disorders
HypocalcemiaMetabolism and nutrition disorders
HypokalemiaMetabolism and nutrition disorders
HypophosphatemiaMetabolism and nutrition disorders
HypothyroidismEndocrine disorders

Most-reported serious reactions: Anemia, Disease progression, Esophageal hemorrhage, Hematuria, Hepatobiliary disorders - Other, hepatobiliary dilatation, Respiratory, thoracic and mediastinal disorders - Other, COVID-19 infection, Stroke, Upper gastrointestinal hemorrhage.

Data from ClinicalTrials.gov NCT04574583 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting TGF-β signal transduction for fibrosis and cancer therapy.
    Peng D, Fu M, Wang M, Wei Y, et al · · 2022 · cited 752× · PMID 35461253 · DOI 10.1186/s12943-022-01569-x
  2. TGF-β signaling in health, disease, and therapeutics.
    Deng Z, Fan T, Xiao C, Tian H, et al · · 2024 · cited 737× · PMID 38514615 · DOI 10.1038/s41392-024-01764-w
  3. Cancer vaccines as promising immuno-therapeutics: platforms and current progress.
    Liu J, Fu M, Wang M, Wan D, et al · · 2022 · cited 497× · PMID 35303904 · DOI 10.1186/s13045-022-01247-x
  4. The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention.
    Cambier S, Gouwy M, Proost P. · · 2023 · cited 387× · PMID 36725964 · DOI 10.1038/s41423-023-00974-6
  5. Targeting cytokine and chemokine signaling pathways for cancer therapy.
    Yi M, Li T, Niu M, Zhang H, et al · · 2024 · cited 264× · PMID 39034318 · DOI 10.1038/s41392-024-01868-3
  6. Exploiting innate immunity for cancer immunotherapy.
    Yi M, Li T, Niu M, Mei Q, et al · · 2023 · cited 151× · PMID 38008741 · DOI 10.1186/s12943-023-01885-w
  7. Emerging strategies in targeting tumor-resident myeloid cells for cancer immunotherapy.
    Wang Y, Johnson KCC, Gatti-Mays ME, Li Z. · · 2022 · cited 103× · PMID 36031601 · DOI 10.1186/s13045-022-01335-y
  8. Combined Inhibition of SHP2 and CXCR1/2 Promotes Antitumor T-cell Response in NSCLC.
    Tang KH, Li S, Khodadadi-Jamayran A, Jen J, et al · · 2022 · cited 94× · PMID 34353854 · DOI 10.1158/2159-8290.cd-21-0369

Verify or expand the search:

Other trials of SX-682

Trials testing the same drug.

Other recruiting trials for Metastatic Cancer

Currently open trials in the same condition.

Other National Cancer Institute (NCI) trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04574583.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing