RBS2418 Evaluation in Subjects With Unresectable or Metastatic Tumors
RBS2418 Evaluation in Subjects With Unresectable or Metastatic Tumors
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 checkpoint blockade. This study is an
open-label, multi-site Phase 1a/1b study of RBS2418, a selective ENPP1 inhibitor, in
combination with pembrolizumab or as a monotherapy in subjects with advanced unresectable,
recurrent or metastatic tumors.
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 checkpoint blockade. This study is an
open-label, multi-site Phase 1a/1b study of RBS2418, a selective ENPP1 inhibitor, in
combination with pembrolizumab or as a monotherapy in subjects with advanced unresectable,
recurrent or metastatic tumors.
Phase I
Phase I
Adults
Mol. targeted/Immunotherapy/Biologics
MK-3475,
Pembrolizumab (MK-3475),
RBS2418
Berlin, Jordan
International
Vanderbilt University
01-23-2024
Eligibility
18 Years
BOTH
NO
Inclusion Criteria:
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.
18 years of age on day of signing informed consent.
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 treatment known to confer significant clinical benefit.
Have histologically or cytologically confirmed cancer diagnosis based on pathology report.
Have a predicted life expectancy of greater or equal to 3 months.
Have measurable disease based on RECIST 1.1.
Have a performance status of 0, 1 or 2 using the ECOG Performance Scale within 14 days of first dose of study drug.
Willing to submit a pre-treatment (archival or fresh-tissue if no archival is available) and on-treatment tissue sample for intra-tumoral ENPP1 assessment. 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.
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.
Demonstrate adequate organ function: hematological, renal, hepatic, coagulation parameters and obtained within 14 days prior to the first study treatment
Exclusion Criteria:
Any approved anti-cancer therapy including chemotherapy, targeted small molecule therapy or radiation therapy within 2 weeks prior to trial Day 1; 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
Subjects with evidence of rapid progression on prior therapy resulting in rapid clinical deterioration should be excluded from participation in the trial.
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.
Uncontrolled tumor-related pain
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
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-nave for indolent tumors
Treatment with systemic immunomodulating agents (including but not limited to Interferons (IFNs), Interleukin-2 (IL-2), anti-PD-1/PD-L1 inhibitors, ipilimumab) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to first dose.
History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
Known hypersensitivity allergy or contraindication to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the PD-1/PD-L1 inhibitor formulation.
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).
History or any evidence of interstitial lung disease
Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment.
Active HIV requiring therapy and Uncontrolled HIV*. HIV antibody testing recommended per investigator's clinical suspicion.
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.
Received therapeutic oral or IV antibiotics within 2 weeks prior to Day 1
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
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.
18 years of age on day of signing informed consent.
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 treatment known to confer significant clinical benefit.
Have histologically or cytologically confirmed cancer diagnosis based on pathology report.
Have a predicted life expectancy of greater or equal to 3 months.
Have measurable disease based on RECIST 1.1.
Have a performance status of 0, 1 or 2 using the ECOG Performance Scale within 14 days of first dose of study drug.
Willing to submit a pre-treatment (archival or fresh-tissue if no archival is available) and on-treatment tissue sample for intra-tumoral ENPP1 assessment. 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.
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.
Demonstrate adequate organ function: hematological, renal, hepatic, coagulation parameters and obtained within 14 days prior to the first study treatment
Exclusion Criteria:
Any approved anti-cancer therapy including chemotherapy, targeted small molecule therapy or radiation therapy within 2 weeks prior to trial Day 1; 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
Subjects with evidence of rapid progression on prior therapy resulting in rapid clinical deterioration should be excluded from participation in the trial.
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.
Uncontrolled tumor-related pain
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
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-nave for indolent tumors
Treatment with systemic immunomodulating agents (including but not limited to Interferons (IFNs), Interleukin-2 (IL-2), anti-PD-1/PD-L1 inhibitors, ipilimumab) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to first dose.
History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
Known hypersensitivity allergy or contraindication to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the PD-1/PD-L1 inhibitor formulation.
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).
History or any evidence of interstitial lung disease
Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment.
Active HIV requiring therapy and Uncontrolled HIV*. HIV antibody testing recommended per investigator's clinical suspicion.
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.
Received therapeutic oral or IV antibiotics within 2 weeks prior to Day 1
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
