RECRUITING

Evaluation of RBS2418 in Subjects With Advanced, Metastatic Solid Tumors

Conditions

Advanced Cancer Metastatic tumors Recurrent tumors Unresectable tumors

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

RBS2418 (investigational product) is a specific immune modulator, working through ectonucleotide pyrophosphatase/phosphodiesterase I (ENPP1), designed to lead to anti-tumor immunity by increasing endogenous 2'-3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) and adenosine triphosphate (ATP levels) and reducing adenosine production in the tumors. RBS2418 has the potential to be an important therapeutic option for subjects both as monotherapy and in combination with other cancer treatments including monotherapy and in combination with other cancer treatments including immunotherapy or chemotherapy. This study is an open-label, multi-site Phase 1a/1b study of RBS2418, a selective ENPP1 inhibitor, in combination with pembrolizumab or other approved anticancer therapies or as a monotherapy in subjects with advanced unresectable, recurrent or metastatic tumors. The phase 1a (dose escalation phase) has been completed. The Phase 1b expansion phase of the study has been increased in size and scope.

Official Title

A First-In-Human, Phase 1 a/b Dose Escalation and Expansion Study to Evaluate RBS2418 as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced Unresectable, Recurrent or Metastatic Tumors

Quick Facts

Study Start:2022-07-11

Study Completion:2027-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05270213

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Be willing and able to provide written informed consent for the study. The subject may also provide consent for Future biomedical research (FBR). However, the subject may participate in the main study without participating in FBR. 2. 18 years of age on day of signing informed consent. 3. Male and female subjects with advanced unresectable, recurrent or metastatic tumors who have received standard of care (SOC) therapy for their advanced/metastatic tumors and have no other SOC therapy available. Additionally, subjects must have received, have been intolerant to, have been ineligible for, or have declined all SOC therapies known to confer significant clinical benefit. 4. Have histologically or cytologically confirmed cancer diagnosis based on pathology report. 5. Have a predicted life expectancy of greater or equal to 3 months. 6. Have measurable disease based on RECIST 1.1. 7. Have a performance status of 0, 1 or 2 using the ECOG Performance Scale within 14 days of first dose of study drug. 8. Willing to submit a pre-treatment (archival or fresh-tissue if no archival tissue is available) and on-treatment tissue sample. Subjects in whom the treating physician deems such biopsy is clinically contraindicated will be evaluated on a case-by-case basis for enrollment pending Sponsor consultation. 9. Have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study drug (female subjects of childbearing potential who are not surgically sterilized or postmenopausal). If the urine test is positive, or cannot be confirmed as negative, a serum pregnancy test will be required. 10. Demonstrate adequate organ function: hematological, renal, hepatic, coagulation parameters and obtained within 14 days prior to the first study treatment 11. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use two highly effective contraceptive methods that result in a combined failure rate of \< 1% per year during the treatment period and for at least 120 days after the last dose of study treatment or as instructed by the package insert of the chosen co-medication. 12. For male subjects: Agree that during the period specified above, men will not father a child. Male subjects must remain abstinent (refrain from heterosexual intercourse with women of childbearing potential), must be surgically sterile (e.g., vasectomy) or use contraceptive methods that result in a failure rate of \< 1% per year during the treatment period and for at least 120 days after the last dose of study treatment.	1. Use of any systemic anti-cancer therapy (including radiotherapy, chemotherapy, targeted therapy or immunotherapy) within 2 weeks prior to first dose of RBS2418 unless such therapy is being administered in combination with RBS2418 per protocol and has been approved by the Sponsor; or if subject has not recovered (i.e., Less than or equal to Grade 1 or returned to baseline level) from adverse events due to a previously administered agent; the following exceptions are allowed: * Palliative radiotherapy for bone metastases or soft tissue lesions should be completed \> 7 days prior to baseline imaging * Hormone-replacement therapy or oral contraceptives * Subjects with Grade 2 neuropathy or Grade 2 alopecia 2. Subjects with evidence of rapid progression on prior therapy resulting in rapid clinical deterioration should be excluded from participation in the trial. 3. Currently participating and receiving trial therapy or has participated in a trial of an investigational agent and/or has used an investigational device within 28 days prior to Day 1. 4. Uncontrolled tumor-related pain 5. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures 6. Malignancies other than indications open for enrollment within 3 years prior to Day 1, with the exception of those with negligible risk of metastasis or death treated with expected curative outcome, undergoing active surveillance or treatment-naïve for indolent tumors 7. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins. 8. Known hypersensitivity allergy or contraindication to any investigational product components administered as part of the combination therapy. 9. Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). 10. History or any evidence of interstitial lung disease 11. Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment. 12. Active HIV requiring therapy and Uncontrolled HIV\. HIV antibody testing recommended per investigator's clinical suspicion. 13. Active hepatitis B virus (HBV; hepatitis B surface antigen reactive) or active hepatitis C virus (HCV; qualitative RNA detected)\; such as requiring active therapy (e.g. subjects with a history of HCV are eligible as long as viral RNA is below level of detection); testing recommended per investigator's clinical suspicion. 14. Severe infections within 4 weeks prior to enrollment, including, but not limited to, hospitalization for complications of infection, bacteremia, or the presence of any active infection requiring systemic therapy. 15. Received therapeutic oral or IV antibiotics within 2 weeks prior to Day 1 16. History or current evidence of any condition, therapy, or laboratory abnormality that in the opinion of the treating investigator might confound the results of the trial or interfere with the subject's participation for the full duration of the trial. 17. Subjects with: * A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval of \> 480 milliseconds (ms) (CTCAE Grade 1) using Fridericia's QT correction formula * A history of additional risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) * The use of concomitant medications that are known to prolong the QT/QTc interval unless there is evidence of the lack of QT/QTc interval prolongation at baseline. 18. Subjects with gastrointestinal disorders that may affect the absorption of the drug 19. Prior allogeneic stem cell or solid organ transplant. 20. Received a live, attenuated vaccine within 28 days prior to enrollment/cohort assignment or anticipation that such a live attenuated vaccine will be required during the trial 21. Known previous or ongoing, active psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 22. Prisoner or subject who is compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (i.e. infectious disease) illness. 23. Pregnant or lactating or intending to become pregnant or father children within the projected duration of the trial starting with the screening visit through 120 days after the last dose of pembrolizumab and/or RBS2418.

Inclusion Criteria

Exclusion Criteria

1. Be willing and able to provide written informed consent for the study. The subject may also provide consent for Future biomedical research (FBR). However, the subject may participate in the main study without participating in FBR.
2. 18 years of age on day of signing informed consent.
3. Male and female subjects with advanced unresectable, recurrent or metastatic tumors who have received standard of care (SOC) therapy for their advanced/metastatic tumors and have no other SOC therapy available. Additionally, subjects must have received, have been intolerant to, have been ineligible for, or have declined all SOC therapies known to confer significant clinical benefit.
4. Have histologically or cytologically confirmed cancer diagnosis based on pathology report.
5. Have a predicted life expectancy of greater or equal to 3 months.
6. Have measurable disease based on RECIST 1.1.
7. Have a performance status of 0, 1 or 2 using the ECOG Performance Scale within 14 days of first dose of study drug.
8. Willing to submit a pre-treatment (archival or fresh-tissue if no archival tissue is available) and on-treatment tissue sample. Subjects in whom the treating physician deems such biopsy is clinically contraindicated will be evaluated on a case-by-case basis for enrollment pending Sponsor consultation.
9. Have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study drug (female subjects of childbearing potential who are not surgically sterilized or postmenopausal). If the urine test is positive, or cannot be confirmed as negative, a serum pregnancy test will be required.
10. Demonstrate adequate organ function: hematological, renal, hepatic, coagulation parameters and obtained within 14 days prior to the first study treatment
11. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use two highly effective contraceptive methods that result in a combined failure rate of \< 1% per year during the treatment period and for at least 120 days after the last dose of study treatment or as instructed by the package insert of the chosen co-medication.
12. For male subjects: Agree that during the period specified above, men will not father a child. Male subjects must remain abstinent (refrain from heterosexual intercourse with women of childbearing potential), must be surgically sterile (e.g., vasectomy) or use contraceptive methods that result in a failure rate of \< 1% per year during the treatment period and for at least 120 days after the last dose of study treatment.

1. Use of any systemic anti-cancer therapy (including radiotherapy, chemotherapy, targeted therapy or immunotherapy) within 2 weeks prior to first dose of RBS2418 unless such therapy is being administered in combination with RBS2418 per protocol and has been approved by the Sponsor; or if subject has not recovered (i.e., Less than or equal to Grade 1 or returned to baseline level) from adverse events due to a previously administered agent; the following exceptions are allowed:
* Palliative radiotherapy for bone metastases or soft tissue lesions should be completed \> 7 days prior to baseline imaging
* Hormone-replacement therapy or oral contraceptives
* Subjects with Grade 2 neuropathy or Grade 2 alopecia
2. Subjects with evidence of rapid progression on prior therapy resulting in rapid clinical deterioration should be excluded from participation in the trial.
3. Currently participating and receiving trial therapy or has participated in a trial of an investigational agent and/or has used an investigational device within 28 days prior to Day 1.
4. Uncontrolled tumor-related pain
5. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
6. Malignancies other than indications open for enrollment within 3 years prior to Day 1, with the exception of those with negligible risk of metastasis or death treated with expected curative outcome, undergoing active surveillance or treatment-naïve for indolent tumors
7. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
8. Known hypersensitivity allergy or contraindication to any investigational product components administered as part of the combination therapy.
9. Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
10. History or any evidence of interstitial lung disease
11. Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment.
12. Active HIV requiring therapy and Uncontrolled HIV\*. HIV antibody testing recommended per investigator's clinical suspicion.
13. Active hepatitis B virus (HBV; hepatitis B surface antigen reactive) or active hepatitis C virus (HCV; qualitative RNA detected)\*; such as requiring active therapy (e.g. subjects with a history of HCV are eligible as long as viral RNA is below level of detection); testing recommended per investigator's clinical suspicion.
14. Severe infections within 4 weeks prior to enrollment, including, but not limited to, hospitalization for complications of infection, bacteremia, or the presence of any active infection requiring systemic therapy.
15. Received therapeutic oral or IV antibiotics within 2 weeks prior to Day 1
16. History or current evidence of any condition, therapy, or laboratory abnormality that in the opinion of the treating investigator might confound the results of the trial or interfere with the subject's participation for the full duration of the trial.
17. Subjects with:
* A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval of \> 480 milliseconds (ms) (CTCAE Grade 1) using Fridericia's QT correction formula
* A history of additional risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
* The use of concomitant medications that are known to prolong the QT/QTc interval unless there is evidence of the lack of QT/QTc interval prolongation at baseline.
18. Subjects with gastrointestinal disorders that may affect the absorption of the drug
19. Prior allogeneic stem cell or solid organ transplant.
20. Received a live, attenuated vaccine within 28 days prior to enrollment/cohort assignment or anticipation that such a live attenuated vaccine will be required during the trial
21. Known previous or ongoing, active psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
22. Prisoner or subject who is compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (i.e. infectious disease) illness.
23. Pregnant or lactating or intending to become pregnant or father children within the projected duration of the trial starting with the screening visit through 120 days after the last dose of pembrolizumab and/or RBS2418.

Contacts and Locations

Study Contact

Riboscience Clinical Trials

CONTACT

‪(415) 754-3182‬

clinicaltrials@riboscience.com

Principal Investigator

Riboscience Chief Medical Officer

STUDY_DIRECTOR

Riboscience, LLC.

Study Locations (Sites)

Honor Health Research Institute

Scottsdale, Arizona, 85258

United States

University of Arizona

Tucson, Arizona, 85724

United States

Stanford Cancer Institute

Palo Alto, California, 94305

United States

UCLA Hematology/Oncology - Santa Monica

Santa Monica, California, 90404

United States

Christiana Care Health Services

Newark, Delaware, 19713

United States

Norton Cancer Institute

Louisville, Kentucky, 40202

United States

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121

United States

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21224

United States

American Oncology Partners of Maryland

Bethesda, Maryland, 20817

United States

Ichan School of Medicine at Mount Sinai

New York, New York, 10029

United States

Carolina BioOncology Institute

Huntersville, North Carolina, 28078

United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37235

United States

Tranquil Research

Webster, Texas, 77598

United States

NEXT Virigina

Fairfax, Virginia, 22031

United States

Collaborators and Investigators

Sponsor: Riboscience, LLC.

Riboscience Chief Medical Officer, STUDY_DIRECTOR, Riboscience, LLC.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-07-11

Study Completion Date2027-12

Study Record Updates

Study Start Date2022-07-11

Study Completion Date2027-12

Terms related to this study

Keywords Provided by Researchers

Metastatic tumors
Recurrent tumors
Unresectable tumors

Additional Relevant MeSH Terms

Advanced Cancer