Clinical Trial 23460

• Overview

  Study Title:

  A Multicenter Phase I/Ib Dose Escalation Study of WTX-124 as Monotherapy and in Combination with Pembrolizumab in Patients with Selected Advanced or Metastatic Solid Tumors

  Objective:

  Primary Objectives: *To determine the MTD and/or recommended dose for expansion (RDE) and evaluate the safety and tolerability of WTX-124 *To determine the MTD and/or RDE and evaluate the safety and tolerability of WTX-124 in combination with pembrolizumab *To further characterize the safety of WTX-124 when administered as monotherapy and in combination with pembrolizumab *To evaluate the antitumor activity of WTX-124 monotherapy in advanced or metastatic renal clear cell carcinoma, cutaneous malignant melanoma and cutaneous squamous cell carcinoma *To evaluate the antitumor activity of WTX-124 in combination with pembrolizumab in advanced or metastatic renal clear cell carcinoma and cutaneous malignant melanoma Secondary Objectives: *To characterize the PK profile of WTX-124 (parent compound and free IL-2) *To evaluate the antitumor activity of WTX-124 (as a monotherapy and in combination with pembrolizumab) in the Dose Escalation *To evaluate changes in certain immunological biomarkers in blood and in baseline and post-treatment tumor biopsies in response to WTX-124 as monotherapy or in combination with pembrolizumab *To evaluate the antitumor activity of WTX-124 as a monotherapy in advanced or metastatic renal clear cell carcinoma, cutaneous malignant melanoma and cutaneous squamous cell carcinoma in the Dose Expansion *To evaluate the antitumor activity of WTX-124 in combination with pembrolizumab in advanced or metastatic renal clear cell carcinoma or cutaneous malignant melanoma in the Dose Expansion *Quantify the duration of response in patients who discontinue therapy following a complete response to WTX-124 *To evaluate the immunogenicity of WTX-124, including the potential to generate an antidrug antibody (ADA) response *To evaluate overall survival (OS)

• Treatments

  Therapies:

  Immunotherapy; Therapy (NOS)

  Medications:

  Pembrolizumab (Keytruda)

• Inclusion Criteria

  Key Inclusion Criteria:
  • Able to understand and voluntarily sign a written informed consent form (ICF) and is willing and able to comply with protocol requirements;
  • Body weight minimum of 35 kg
  • Has histological or cytological documentation of a solid tumor indication for which a CPI (e.g. anti-PD-(L)1 is indicated (e.g., malignant melanoma, non-small cell lung cancer, small cell lung cancer, head and neck squamous cell cancer, urothelial cancer, microsatellite instabilityhigh or mismatch repair deficient cancer, microsatellite -instability high- or mismatch repair deficient colorectal cancer, gastric cancer, esophageal cancer, cervical cancer, hepatocellular carcinoma, Merkel cell carcinoma, renal clear cell carcinoma, endometrial carcinoma, tumor mutational burden-high cancer, cutaneous squamous cell carcinoma, advanced basal cell carcinoma) for all parts of the clinical study;
  • Monotherapy Dose Escalation: Patients with relapsed/refractory locally advanced or metastatic solid tumors for which immunotherapy is approved, who have progressed on or are intolerant to standard therapy, including CPIs, or for whom no standard therapy with proven benefit exists; Combination Dose Escalation: Patients with relapsed/refractory locally advanced or metastatic solid tumors for which immunotherapy is approved, who have progressed on or are intolerant to standard therapy or for whom no standard therapy with proven benefit exists. Patients must have progressed on prior CPI therapy as defined by RECIST 1.1 or iRECIST or discontinued for reasons other than toxicity.
  • ≥18 years of age;
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
  • HIV infected participants must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease defined within the protocol;
  • Has at least 1 measurable lesion per RECIST 1.1 (lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions);
  • Agrees to undergo a pre-treatment and post-treatment biopsy of a primary or metastatic solid tumor lesion;
  • Has adequate organ and bone marrow function defined within the protocol;
  • Willingness of men and women of reproductive potential to observe highly effective birth control for the duration of treatment and for 4 months following the last dose of study drug;
  • Other criteria may apply.

• Exclusion Criteria

  Key Exclusion Criteria:
  • Have a history of another active malignancy (a second cancer) within the previous 2 years except for localized cancers that are not related to the current cancer being treated, are considered cured, and, in the opinion of the Investigator, presents a low risk of recurrence. These exceptions include, but are not limited to, basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast;
  • Combination therapy: Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease; Monotherapy: has current pneumonitis / interstitial lung disease;
  • Have a diagnosis of uveal or mucosal melanoma in Dose Expansion Phase arms;
  • Have received prior IL-2 therapy (e.g., high dose IL-2 or investigational IL-2 therapies);
  • Have had an allogeneic tissue/solid organ transplant;
  • Have known symptomatic brain metastases requiring steroids. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment, have recovered from the acute effects of radiation therapy or surgery prior to enrollment, and are neurologically stable and asymptomatic;
  • Have significant cardiovascular disease, including myocardial infarction, arterial thromboembolism, or cerebrovascular thromboembolism, within 6 months prior to the first dose of study drug; symptomatic dysrhythmias or unstable dysrhythmias requiring medical therapy; angina requiring therapy; symptomatic peripheral vascular disease; New York Heart Association Class 3 or 4 congestive heart failure; or history of congenital prolonged QT syndrome;
  • Have significant electrocardiogram (ECG) abnormalities at Screening, including unstable cardiac arrhythmia requiring medication, left bundle branch block, second-degree atrioventricular block type II, third-degree AV block, ≥Grade 2 bradycardia, or QT interval corrected for heart rate using Fridericia’s formula (QTcF) >470 msec;
  • Have an active autoimmune disease that required systemic treatment in the past 2 years (i.e., with use of disease-modifying antirheumatic agents or immunosuppressive drugs);
  • Diagnosis of immunodeficiency, is on immunosuppressive therapy, or is receiving chronic systemic or enteric steroid therapy (dose >10 mg/day of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug;
  • Major surgery (excluding placement of vascular access) within 2 weeks prior to the first dose of study drug;
  • Investigational agent or anticancer therapy (including chemotherapy, biologic therapy, immunotherapy, anticancer Chinese medicine, or other anticancer herbal remedy) within 5 half-lives or 4 weeks (whichever is shorter) prior to the first dose of study drug. In addition, no concurrent investigational anticancer therapy is permitted;
  • Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
  • Any unresolved toxicities from prior therapy greater than NCI CTCAE version 5.0 Grade 1 at the time of starting study drug except for alopecia, Grade 2 platinum therapy-related neuropathy and Grade 2 endocrine immune-related AEs managed with a stable dose of hormone replacement;
  • Other criteria may apply.

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