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RBS2418 Evaluation in Subjects With Unresectable or Metastatic Tumors


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Trial ID: NCT05270213


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.

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


Inclusion 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 treatment
   known to confer significant clinical benefit.

   4. Have histologically or cytologically confirmed cancer diagnosis based on pathology

   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 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.

   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

Exclusion Criteria:

   1. 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

      - 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. 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

   8. History of severe allergic, anaphylactic, or other hypersensitivity reactions to
   chimeric or humanized antibodies or fusion proteins.

   9. Known hypersensitivity allergy or contraindication to biopharmaceuticals produced in
   Chinese hamster ovary cells or any component of the PD-1/PD-L1 inhibitor formulation.

10. Active autoimmune disease that has required systemic treatment in the past 2 years
   (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive

11. History or any evidence of interstitial lung disease

12. Treatment with systemic immunosuppressive medication within 2 weeks prior to
   initiation of study treatment.

13. Active HIV requiring therapy and Uncontrolled HIV*. HIV antibody 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. 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


drug: RBS2418


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Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Feriel Buchholz
+1 650-721-4090