Clinical Trial 23475

• Overview

  Study Title:

  A Phase 1/2 Study of OR502 Alone and in Combination with other Anti-cancer Agents in Subjects with Advanced Malignancies

  Summary:

  This is an open-label, multicenter, first-in-human dose-escalation and expansion Phase 1-2 study designed to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of OR502 administered as a monotherapy and in combination with cemiplimab in patients with advanced solid tumors.

  Objective:

  Part A Primary: * To evaluate the safety and tolerability of OR502 when given alone or in combination with cemiplimab to subjects with advanced solid tumors * To determine the recommended dose(s) and regimen(s) of OR502 when given alone or in combination with cemiplimab for further development Part A Secondary: * To characterize the serum pharmacokinetics (PK) of OR502 when given alone or in combination with cemiplimab to subjects with advanced solid tumors Part B Primary: * To further evaluate the safety and tolerability of OR502 when given alone or in combination with cemiplimab to subjects with advanced solid tumors, platinum-resistant ovarian cancer (PROC), or cutaneous squamous cell carcinoma (CSCC) * To determine the dose of OR502 to be used for further development Part B Secondary: * To assess the anti-tumor activity of OR502 when given alone or in combination with cemiplimab to subjects with advanced solid tumors, PROC, or CSCC * To characterize the serum PK of OR502 when given alone or in combination with cemiplimab to subjects with advanced solid tumors, PROC, or CSCC * To characterize the immunogenicity of OR502 when given alone or in combination with cemiplimab to subjects with advanced solid tumors, PROC, or CSCC

• Treatments

  Therapies:

  Immunotherapy

  Medications:

  Cemiplimab (); OR502 (); REGN2810 (Cemiplimab)

• Inclusion Criteria

  Inclusion Criteria:
  • Informed consent signed by the patient prior to conducting study-specific procedure
  • Male or female ages 18 or older
  • Histological diagnosis as follows: Parts A and B (Cohorts A1, A2, and B1): patients must have a histological diagnosis of any type of carcinoma, sarcoma, or melanoma with progressive metastatic disease, or progressive locally advanced disease not amenable to local therapy with curative intent. Part B (Expansion Cohorts B2-B3): patients must have a histological diagnosis of the relevant tumor type (CSCC or PROC) with advanced/metastatic disease not amenable to local therapy with curative intent.
  • Prior therapies: a. Part A (dose-escalation) and Cohort B1 (monotherapy expansion) i. patients must have experienced progressive disease (PD) on an established standard systemic anti-cancer therapy for a given tumor type or have been intolerant to such therapy, or in the opinion of the Investigator have been considered ineligible for a particular form of standard therapy on medical grounds. Patients must have no available proven curative or life prolonging therapies. b. Cohorts B4 and B5 (mini-expansion cohorts) i. Patients must have received a PD-(L)1 inhibitor-based therapy, either alone or in combination with other anti-cancer agents, for at least 12 weeks. If patients have received other lines of immunotherapy, including PD-(L)1-based therapy, they must have demonstrated clinical benefit on each prior immunotherapy. Patients may also have received additional anti-cancer therapies after failure of a PD-(L)1 inhibitor, but 2nd line patients are preferred. c. Cohorts B2 and B3 (dose-expansion) i. Cohort B2 (CSCC) must have received a PD-(L)1 inhibitor. Patient may not have received an additional immunotherapy. ii. Cohort B3 patients (PROC) must have received platinum-based therapy and experienced disease progression on or within 6 months of completion of such therapy. Patient may have received prior anti-PD-1 therapy. Patient may have received additional therapies after failure of platinum-based therapy.
  • Must have measurable disease per RECIST v1.1.
  • Patients of childbearing potential, if not postmenopausalor surgically sterile, must be willing to practice at least one of the highly effective methods of birth control described in Section 4.3 for at least a menstrual cycle (or partner's menstrual cycle, for male patients) before & for 4 months after study medication administration.
  • Resolution of prior clinically significant therapy-related AEs (excluding alopecia and Grade 2 peripheral neuropathy) to Grade 1 or less and no treatment for these AEs for at least 2 weeks prior to the time of enrollment. Electrolyte and hormonal supplementation may be used to treat these AEs provided the patient is stable on these supplements.
  • Minimum of 2 weeks since last dose of other hormone therapy & 3 weeks since the last dose of other systemic cancer therapy or radiotherapy (> 4 weeks in case of nitrosoureas or radio-immuno conjugate therapy). Adjuvant hormonal therapy (e.g., tamoxifen) is allowed provided the original tumor diagnosis was more than 3 years before the first dose of study medication. Patients with prostate cancer on stable doses of anti-hormone treatment may remain on therapy for this trial.
  • Adequate organ function.
  • Biopsy specimens: All patients must be able to supply an archival tumor tissue specimen. If an archival specimen is not available, patient may remain eligible with approval of the medical monitor.
  • Patients in Cohort B1 must consent to pre- and on-treatment biopsies. Tissue obtained for the biopsy must not be previously irradiated. No systemic anti-neoplastic therapy may be received by the patient between the time of the biopsy and the first administration of study medication.
  • Additional criteria apply

• Exclusion Criteria

  Exclusion Criteria:
  • Previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb).
  • Life expectancy less than 12 weeks.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) > 2.
  • Prior organ or stem cell transplant.
  • Patients with symptomatic ascites or pleural effusion. Patients who are clinically stable for at least 2 weeks following treatment for these conditions are eligible.
  • Known active central nervous system (CNS) primary tumor or metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks prior to study entry, have no radiological evidence of new or enlarging brain metastases, and are off steroids or on a stable dose up to an equivalent of prednisone 10 mg/day for at least 15 days prior to first dose of study medication. Patients who have symptoms consistent with CNS metastasis must have a negative magnetic resonance imaging (MRI) scan during the screening period.
  • Known history of a hematologic malignancy, malignant primary brain tumor, or another malignant primary solid tumor (other than that under study), unless the subject has undergone potentially curative therapy with no evidence of recurrent disease for at least 3 years before the start of treatment.
  • Known history of AJCC Stage 1 cancer that has undergone potentially curative therapy with no evidence of recurrent disease for at least 1 year before the start of treatment may be eligible at the Investigator's discretion after consultation with the Sponsor.
  • Underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers at any time before the start of treatment, and have no evidence of recurrent disease, are eligible.
  • Recent or ongoing serious infection including the following: (1) Any uncontrolled Grade 3 or higher (per NCI-CTCAE version 5.0) viral, bacterial, or fungal infection within 2 weeks prior to the first dose of OR502. Routine antimicrobial prophylaxis is allowed. (2) Uncontrolled infection with human immunodeficiency virus (HIV). Patients on stable highly active antiretroviral therapy (HAART) with undetectable viral load and normal CD4 counts for at least 6 months prior to study entry are eligible. Serological testing for HIV at screening is not required. (3) Known to be positive for hepatitis B virus (HBV) surface antigen, or any other positive test for hepatitis B indicating acute or chronic infection. Patients who are or have received anti-HBV therapy and have undetectable HBV DNA for at least 6 months prior to study entry are eligible. Serological testing for hepatitis B at screening is not required.(4) Known active hepatitis C as determined by positive serology and confirmed by polymerase chain reaction (PCR). Patients on or having received anti-retroviral therapy are eligible provided they are virus-free by PCR for at least 6 months prior to study entry. Serological testing for hepatitis C at screening is not required. (5) Known active or latent tuberculosis (testing at screening is not required).
  • Autoimmune disease or inflammatory condition requiring systemic anti-inflammatory therapy with exceptions as noted below. Patients on hormone replacement therapy for autoimmune-induced endocrinopathies are eligible.
  • Use of systemic corticosteroids within 15 days or other immunosuppressive drugs within 30 days prior to start of the study, with the exception of corticosteroids as replacement therapy up to an equivalent of prednisone 10 mg/day, which are allowed.
  • Has received a live vaccine within 30 days prior to first administration of study medication.
  • Other criteria apply

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