Phase 2
Completed N=12
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)
Source: ClinicalTrials.gov NCT04574583 ↗Enrolled (actual)
12
Serious AEs
41.7%
Results posted
May 2023
Primary outcomePrimary: Dose Limiting Toxicities (DLT) — 0; 1; 0 toxicities
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Dose Limiting Toxicities (DLT) |
0; 1; 0 | — |
| PRIMARY Number of Participants With Grades 3-5 Adverse Events (AEs) Related and/or Unrelated to SX-682 + BinTrafusp Alfa (M7824) + BN-CV301 |
2; 2; 2; 0; 0; 0 | — |
| PRIMARY Maximum Tolerated Dose (MTD) of SX-682 Followed by BinTrafusp Alfa (M7824) and CV301 Vaccines in Participants With Advanced or Metastatic Solid Tumors. |
NA | — |
| PRIMARY Recommended Phase II Dose (RP2D) of SX-682 With BinTrafusp Alfa (M7824) and CV301 Vaccines in Participants With Advanced or Metastatic Solid Tumors. |
NA | — |
| PRIMARY Percentage of Participants Who Experience a Response |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants Disease Control Rate (DCR): Complete Response (CR)+ Partial Response (PR) + Stable Disease (SD) |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Progression-free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors (RECIST)1.1. |
2.0; 3.4; 1.8 | — |
| SECONDARY Pharmacokinetic Profile of SX-682 as a Single Agent and in Combination |
NA; 7.88; 17.7; 104; 124; 105 | — |
| SECONDARY Pharmacodynamic Profile of SX-682 as a Single Agent and in Combination |
— | — |
Eligibility Criteria
- INCLUSION CRITERIA:
- Participants must have histologically or cytologically confirmed:
- Metastatic or locally advanced, Solid tumor (Cohort 1)
OR
--Metastatic or locally recurrent, non-resectable Triple Negative Breast Cancer (TNBC), defined as estrogen receptor (ER) 1,500/mcL
- Platelets >100,000/mcL
- Hemoglobin > 9 g/dL without a blood transfusion in the 14 days prior to enrollment.
- Total bilirubin 60 mL/min/1.73 m^2 using the Cockcroft-Gault calculation (https://www.kidney.org/professionals/KDOQI/gfr\_calculatorCoc).
- The effects of immunotherapies on the developing human fetus are unknown. For this reason and because immunotherapy agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) at the time of study entry, for the duration of study treatment and up to 6 months after the last dose of the study drug (s). Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- Participants with well-controlled human immunodeficiency virus (HIV) infection are eligible for trial as long as:
- On an effective anti-retroviral therapy (ART) > 4 weeks and with evidence of viral suppression defined as HIV viral load 200 cells/microL at enrollment
- No reported opportunistic infections within 6 months prior to enrollment except for the following which will be allowed:
- Esophageal candidiasis treated within last 6 months or currently improving with antifungal treatment
- Oral and/or genital herpes simplex virus (HSV) treated within last 6 months or currently improving with antiviral treatment
- Mycobacterium avium infection in last 6 months or that has been treated for at least 1month.
- Immunomodulating drugs must be discontinued at least 1 weeks prior to enrollment for recent short course use (less than or equal to 14 days) or discontinued at least 4 weeks prior to enrollment for long term use (> 14 days).
- Participants must have a received their last treatment > 4 weeks or 5 half-lives of the last treatment drug, whichever is shorter before starting on trial.
- Participants with known history of hepatitis B (HBV) infection are eligible for trial as long as the HBV viral load is undetectable.
- Patients with known history of hepatitis C (HCV) infection must have been treated and cured (viral load is undetectable). For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable or unquantifiable HCV ribonucleic acid (RNA) 12 weeks or longer after definitive treatment completion.
- Subjects must be able to understand and be willing to sign a written informed consent document.
EXCLUSION CRITERIA
- 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 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
- Partici
Data sourced from ClinicalTrials.gov (NCT04574583). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.