Clinical Trial 21749

• Overview

  Study Title:

  Phase 1/2, Open-Label, Dose Escalation and Dose Expansion Study of TransCon TLR7/8 Agonist Alone or in Combination with Pembrolizumab in Participants with Locally Advanced or Metastatic Solid Tumor Malignancies

  Summary:

  The purpose of this study is to evaluate the safety and tolerability, and to define the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of TransCon TLR7/8 Agonist alone or in combination with pembrolizumab.

  Objective:

  Primary Objectives: * To evaluate the safety and tolerability, and To define the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of TransCon TLR7/8 Agonist alone or in combination with pembrolizumab. To evaluate the anti-tumor activity of TransCon TLR7/8 Agonist in combination with pembrolizumab. * Part 3 Neoadjuvant Cohorts (Cohorts 3c and 3d): To evaluate the anti-tumor activity of TransCon TLR7/8 Agonist in combination with pembrolizumab Secondary Objectives: * To evaluate the anti-tumor activity of TransCon TLR7/8 Agonist alone or in combination with pembrolizumab * To characterize the plasma pharmacokinetics (PK) of resiquimod, Odesethyl resiquimod, and total resiquimod (unbound + bound) after IT administration of TransCon TLR7/8 Agonist alone or in combination with pembrolizumab

• Treatments

  Therapies:

  Immunotherapy

  Medications:

  Pembrolizumab (Keytruda); TransCon TLR7/8 Agonist ()

• Inclusion Criteria

  Inclusion Criteria:
  • At least 18 years of age
  • Participants must have histologically confirmed locally advanced, recurrent or metastatic solid tumor malignancies that cannot be treated with curative intent (surgery or radiotherapy).
  • Participants must have progressed on or be intolerant of available standard of care treatment options or have disease for which there is no standard of care treatment available, with the exception of participants enrolling to the neoadjuvant cohorts.
  • Participants must have at least 2 lesions of measurable disease, unless specified otherwise in the selection criteria.
  • Participants must have a willingness to undergo biopsies.
  • Participants must demonstrate adequate organ function within 28 days of Cycle 1 Day 1 (C1D1).
  • Participants must have a life expectancy greater than 12 weeks as determined by the Investigator.
  • Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
  • Participants who have undergone treatment with anti-PD-1, anti-PD-L1, or antiCTLA 4 antibody must have at least 4 weeks from the last dose of antibody and evidence of disease progression per investigator assessment before enrollment.
  • Participants who have previously received an immune checkpoint inhibitor prior to enrollment must have any immune related toxicities resolved to less than or equal to Grade 1 or baseline (prior to the checkpoint inhibitor) to be eligible.
  • Female and male participants of childbearing potential who are sexually active must agree to use highly effective methods of contraception.

• Exclusion Criteria

  Exclusion Criteria:
  • Participants who have been previously treated with a TLR agonist (excluding topical agents for unrelated disease) are not eligible.
  • Other active malignancies within the last 2 years are excluded.
  • Participants who have active autoimmune diseases, regardless of need for immunosuppressive treatment at the time of screening, with the exception of well controlled on physiologic endocrine replacement.
  • Systemic immunosuppressive treatment with the exception for patients on corticosteroid taper (for example, for chronic obstructive pulmonary disease exacerbation). Participants cannot start dosing on study until steroid dose is at or lower than 10 mg per day prednisone or equivalent.
  • Women who are breastfeeding or have a positive serum pregnancy test during screening or within 72 hours prior to C1D1 are not eligible.
  • Participants who have had vaccination with live, attenuated vaccines within 4 weeks of enrollment.
  • Participants who have symptomatic central nervous system metastases.
  • Participants who have a known bleeding disorder that is deemed to place the participant at unacceptable risk for bleeding complications from intratumoral injections or biopsies.
  • Participants who have a known hypersensitivity to any component of TransCon TLR7/8 Agonist or pembrolizumab.
  • Participants who have any uncontrolled bacterial, fungal, viral, or other infection.
  • Participants who have had treatment with any other anti-cancer systemic treatment (approved or investigational) or radiation therapy within 4 weeks of first dosing on study is not allowed.
  • Participants who have significant cardiac disease
  • Participants who have a marked baseline prolongation of QT/QTc (corrected QT) interval (e.g., repeated demonstration of a QTc interval >480 ms (National Cancer Institute NCI) Common Terminology Criteria for Adverse Events [CTCAE] grade 1) using Fredericia's QT correction formula.
  • Participants who have a history of additional risk factors for Torsades de Pointes (TdP) (e.g., heart failure, clinically significant hypokalemia, family history of Long QT Syndrome).
  • Participants who have used concomitant medications that prolong the QT/QTc interval within 14 days of enrollment.
  • Participants who are positive for HIV or with active hepatitis B or C infection.

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