Study of TBio-6517, Given Intratumorally, Alone or in Combination With Pembrolizumab, in Solid Tumors

Overview

About this study

The purpose of this study is to determine the recommended Phase 2 dose (RP2D) of TBio-6517 when administered by direct injection into tumor(s) alone and when combined with pembrolizumab in patients with solid tumors (RIVAL-01).

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Phase 1 Dose Escalation: Have a histologically or pathologically documented, locally-advanced or metastatic solid tumor for which standard curative measures do not exist or are no longer effective, which may include prior immunotherapy. Preferred indications include: MSS-CRC, TNBC, malignant melanoma, cervical adenocarcinoma, and cholangiocarcinoma.
  • Phase 2a Dose Expansion: Have a histologically or cytologically confirmed advanced (metastatic and/or unresectable) solid tumor listed below, that is incurable and for which prior standard treatment has failed:
    • MSS-CRC (Cohort C) patients that have progressed to at least 2 prior lines of systemic therapy which should include irinotecan and oxaliplatin with or without bevacizamab; or
    • TNBC (Cohort D) patients who have failed anthracycline- and taxane-based chemotherapy. TNBC patients with PD-L1 positive tumors must also have failed treatment with PD-1 or PD-L1 targeted therapy.
      • Note: MSS disease is determined by an approved diagnostic test for identification of patients without a microsatellite instability (MSI) positive biomarker. This testing is performed locally.
      • Note: TNBC as defined by the guidelines of American Society of Clinical Oncology(ASCO)/College of American Pathologist(CAP): Estrogen Receptor (ER) < 1% positive tumor nuclei, Progesterone Receptor (PR) < 1% positive tumor nuclei, and negative for HER2 by IHC 1+, 0 or negativity status confirmed by in situ hybridization (ISH).
  • Have measurable disease based on RECIST 1.1 criteria as determined by the Investigator.
    • Note: In the event all measurable disease is situated in a previously irradiated area, these lesions are only considered measurable if progression has been demonstrated post irradiation treatment.
  • Have at least one tumor amenable to safe ITu injections and biopsies.
  • Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Demonstrate adequate organ function:
    • White blood cell (WBC) count ≥ 2,000 cells/mm^3;
    • Absolute neutrophil count (ANC) ≥ 1,000 cells/mm^3
    • Hemoglobin (Hgb) ≥ 8 g/dL or ≥ 4.96 mmol/L;
    • Platelet count ≥ 100,000 platelets/mm3 (untransfused);
    • Total bilirubin ≤ 1.5× Upper Limit of Normal (ULN);
    • Aspartate transaminase (AST), alanine aminotransferase (ALT) ≤ 2.5× ULN;
    • Serum chemistries: Sodium, potassium, and calcium within normal limits (WNL) or Grade 1;
    • Serum creatinine ≤ 1.5× ULN or creatinine clearance ≥ 60 mL/min for patient with creatinine levels > 1.5 × institutional ULN according to Cockcroft-Gault formula;
    • International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5× ULN.
      • Note: patients must be able to suspend anticoagulant therapy for study specific biopsies and intratumoral injections.
  • To prevent risk of environmental shedding, all patients must be willing to use barrier contraception during sexual activity, starting with Day 1 through 6 weeks after the last dose of TBio-6517. Additionally, to prevent pregnancy, patients who are able to conceive or father children must use a highly effective contraception method during sexual activity starting with Screening through 120 days after the last study treatment, including pembrolizumab.
  • Be willing and able to attend protocol-specified visits, complete protocol procedures, and adhere to post-ITu injection care instructions within the informed consent to minimize the risk of transmission to caregivers and close contacts.
  • Be ≥ 18 years of age (or legal age of majority in the jurisdiction) on day of signing informed consent.
  • Have life expectancy of at least 4 months as determined by the Investigator.
  • Patients must be willing to comply with mandatory pre-treatment and on-Treatment biopsies

Exclusion Criteria:

  • Has disease eligible for therapy with curative intent.
  • Has had prior treatment with any oncolytic virus.
  • Has had prior surgery, chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks prior to first dose, or prior anti-cancer monoclonal antibody (mAb) therapy within 45 days prior to study Day 1.
    • Note: Patients are allowed to receive any of the following treatments up to 7 days prior to the first dose:
      • Stereotactic radiosurgery (SRS);
      • Stereotactic body radiation therapy (SBRT); or
      • Ppalliative radiation outside the chest and brain.
  • Has failed to recover (i.e., to ≤ Grade 1 or to baseline status) from clinically relevant or significant adverse events (AEs) associated with prior cancer treatment Note: Except patients with ≤ Grade 2 neuropathy or any grade of alopecia.
  • Has tumor(s) invading a major vascular structure (e.g., carotid artery) or other key anatomical structure (e.g., pulmonary airway) in the event of post-treatment tumor swelling and/or necrosis.
  • Requires use of anti-platelet or anti-coagulant therapy that cannot be safely suspended for per protocol ITu injections or biopsies as per standard of care.
  • Has central nervous system (CNS) metastases that have not been completely resected or completely irradiated and/or carcinomatous meningitis.
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected) virus infection.
  • Has used excluded anti-viral medication (e.g., interferon (IFN)/peg-IFN, ribavirin, etc.) within 14 days of Day 1 and that cannot be suspended throughout the initial TBio-6517 treatment period and for at least 14 days prior to and after each booster dose of TBio-6517 Note: Acyclovir is permitted.
  • Has significant immunodeficiency due to underlying illness (e.g., known HIV/AIDS) or has received systemic immunosuppressive medication including high-dose corticosteroids (e.g., systemic corticosteroids >10 mg prednisone or equivalent), other than protocol required pre-medications, within 4 weeks prior to the first dose of trial treatment. Inhaled steroids and adrenal replacement doses ≤ 10 mg prednisone or equivalent are permitted in the absence of active autoimmune disease.
    • Note: High dose corticosteroids administered for contrast allergy prophylaxis is permitted throughout the trial prior to radiographic scans as long as the first dose of TBio-6517 is at least 7 days after corticosteroid administration.
  • Prior history of myocarditis.
  • Given the potential risk of tachycardia, hypotension, and/or fluid volume loading during or following treatment with oncolytic viruses, patients with the following should be excluded:
    • Symptomatic cardiovascular disease, including but not limited to, significant coronary artery disease (e.g., myocardial infarction or other coronary artery disease requiring angioplasty or stenting) or congestive heart failure within the preceding 12 months;
    • Asymptomatic cardiovascular disease (current or past history) unless cardiology consultation and clearance has been obtained for study participation;
    • New York Heart Association functional class III-IV heart failure on active treatment;
    • Patients who for any other reason cannot tolerate tachycardia, hypotension, and/or fluid volume loading.
  • Has a known additional malignancy except basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer.
  • Is pregnant, currently breastfeeding or intending to breastfeed, or expecting/trying to conceive or father children within the projected duration of the trial, starting with Screening through 120 days after the last dose of study treatment including pembrolizumab.
  • Pulse oximetry of < 90% in room air at rest.
  • Ongoing severe inflammatory skin condition or history of severe eczema requiring prior medical treatment.
  • Has had prior organ transplant.
  • Has evidence of active, non-infectious pneumonitis.
  • Has a history of interstitial lung disease.
  • Has an illness, metabolic dysfunction, physical examination finding, or clinical laboratory finding that gives reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug or that would limit compliance with study requirements.

In addition to above, the following Exclusion Criteria are applicable to patients intending to receive pembrolizumab combination (i.e., Arm B, Cohort C, Cohort D):

  • Has been intolerant to prior PD-1/PD-L1 targeted antibody therapy for which re-treatment would expose the patient to clinically significant risk in the opinion of the Investigator (please obtain Sponsor permission for enrollment of any patient with prior intolerance to anti-PD-1/PD-L1 antibody treatment).
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunemodulating drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered an excluded form of systemic treatment. Has received a live vaccine within 30 days of planned study treatment.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Kabir Mody, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

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Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Mitesh Borad, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

-

Rochester, Minn.

Mayo Clinic principal investigator

Thorvardur Halfdanarson, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

-

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20490405

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