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Trial record 1 of 1 for:    WTX-124
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Dose Escalation Study of WTX-124 as Monotherapy and in Combination With Pembrolizumab (Pembro) in Patients With Selected Advanced or Metastatic Solid Tumors

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ClinicalTrials.gov Identifier: NCT05479812
Recruitment Status : Recruiting
First Posted : July 29, 2022
Last Update Posted : August 5, 2022
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Werewolf Therapeutics, Inc.

Brief Summary:
A first-in-human, Phase I, open-label, multicenter study of WTX-124 administered as monotherapy and in combination with pembrolizumab to patients with advanced solid tumors.

Condition or disease Intervention/treatment Phase
Metastatic Solid Tumor Advanced Solid Tumor Drug: WTX-124 Drug: Pembrolizumab Phase 1

Detailed Description:
This is a first-in-human, Phase I, open-label, multicenter study designed to evaluate the safety, tolerability and preliminary efficacy of WTX-124, a conditionally-activated IL-2 prodrug, when administered as monotherapy and in combination with pembrolizumab, for the treatment of patients with advanced solid tumors. Part 1 of the study is dose escalation of WTX-124, both as monotherapy and in combination with pembrolizumab. Part 2 is comprised of four arms in which WTX-124 will be administered as monotherapy and in combination with pembrolizumab to patients with advanced or metastatic cutaneous malignant melanoma or advanced or metastatic renal cell carcinoma.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : May 20, 2022
Estimated Primary Completion Date : July 1, 2025
Estimated Study Completion Date : July 31, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: WTX-124 monotherapy dose escalation Drug: WTX-124
Investigation Product Monotherapy

Experimental: WTX-124 monotherapy dose expansion in advanced or metastatic cutaneous malignant melanoma Drug: WTX-124
Investigation Product Monotherapy

Experimental: WTX-124 monotherapy dose expansion in advanced or metastatic RCC Drug: WTX-124
Investigation Product Monotherapy

Experimental: WTX-124 in combination with pembrolizumab dose escalation Drug: WTX-124
Investigation Product Monotherapy

Drug: Pembrolizumab
Investigation Product in combination with approved therapy

Experimental: WTX-124 in combo with pembro dose expansion in advanced/metastatic cutaneous malignant melanoma Drug: WTX-124
Investigation Product Monotherapy

Drug: Pembrolizumab
Investigation Product in combination with approved therapy

Experimental: WTX-124 in combination with pembrolizumab dose expansion in advanced or metastatic RCC Drug: WTX-124
Investigation Product Monotherapy

Drug: Pembrolizumab
Investigation Product in combination with approved therapy




Primary Outcome Measures :
  1. Incidence of Dose Limiting Toxicities (DLTs) in monotherapy and combination therapy [ Time Frame: 4 weeks ]
  2. Incidence of treatment emergent adverse events in monotherapy and combination therapy [ Time Frame: 24 months ]
  3. Incidence of changes in clinical laboratory abnormalities in monotherapy and combination therapy [ Time Frame: 24 months ]
  4. Investigator-assessed objective response rate (ORR) per RECIST 1.1 and iORR by iRECIST in monotherapy and combination therapy [ Time Frame: 24 months ]

Secondary Outcome Measures :
  1. Plasma concentrations of WTX-124 and free IL-2 [ Time Frame: 24 months ]
  2. Investigator-assessed objective response rate (ORR) per RECIST 1.1 and iORR by iRECIST in monotherapy and combination therapy [ Time Frame: 24 months ]
  3. Changes in circulating immune cell populations in response to monotherapy and combination therapy [ Time Frame: 24 months ]
  4. Changes in soluble cytokines in response to monotherapy and combination therapy [ Time Frame: 24 months ]
  5. Changes in tumor immune profile in response to monotherapy and combination therapy [ Time Frame: 24 months ]
  6. Investigator-assessed objective response rate (ORR) per RECIST 1.1 and iORR by iRECIST in monotherapy and combination therapy (in advanced or metastatic renal cell carcinoma and advanced or metastatic cutaneous malignant melanoma) [ Time Frame: 24 months ]
  7. Antidrug antibody (ADA) occurrence [ Time Frame: 24 months ]
  8. Duration of response [ Time Frame: 24 months ]
  9. Progression free survival [ Time Frame: 24 months ]
  10. Overall survival [ Time Frame: 36 months ]
  11. To investigate immunological biomarkers in peripheral blood and tumor that may correlate with the treatment outcome of WTX-124 as monotherapy or in combination with pembrolizumab [ Time Frame: 24 months ]
  12. To assess tumor biopsies for potential biomarkers of target engagement and immune pathway activation [ Time Frame: 24 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Each patient must meet all the following criteria to participate in the study:

  1. Has histological or cytological documentation of a solid tumor indication for which a CPI (e.g. anti-PD-(L)1 is indicated for all parts of the clinical study;
  2. ≥18 years of age;
  3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
  4. 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);
  5. Agrees to undergo a pre-treatment and on-treatment biopsy of a primary or metastatic solid tumor lesion;
  6. Has adequate organ and bone marrow function:
  7. 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;
  8. Additional criteria may apply

Exclusion Criteria:

  1. 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;
  2. Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease;
  3. Have received prior IL-2-directed therapy;
  4. Have had an allogeneic tissue/solid organ transplant;
  5. Have known symptomatic brain metastases requiring steroids;
  6. Have significant cardiovascular disease;
  7. Have an active autoimmune disease that required systemic treatment in the past 2 years;
  8. Diagnosis of immunodeficiency, is on immunosuppressive therapy, or is receiving chronic systemic or enteric steroid therapy
  9. Major surgery (excluding placement of vascular access) within 2 weeks prior to the first dose of study drug;
  10. Investigational agent or anticancer therapy within 5 half-lives or 4 weeks (whichever is shorter) prior to the first dose of study drug;
  11. Has received prior radiotherapy within 2 weeks of start of study treatment. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease;
  12. Any unresolved toxicities from prior therapy greater than NCI CTCAE version 5.0 Grade 1 at the time of starting study drug with the exception of alopecia and Grade 2 prior platinum-therapy related neuropathy;
  13. Received a live or live-attenuated vaccine within 30 days of the first dose of study drug; Note: Administration of killed vaccines or other formats are allowed.
  14. Active, uncontrolled systemic bacterial, viral, or fungal infection;
  15. HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease;
  16. Active infection as determined by hepatitis B surface antigen and hepatitis B core antibody, or hepatitis B virus DNA by quantitative polymerase chain reaction (qPCR) testing;
  17. Active infection as determined by hepatitis C virus (HCV) antibody or HCV RNA by qPCR testing;
  18. Pregnant or lactating;
  19. History of hypersensitivity to any of the study drug components;
  20. Additional criteria may apply.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05479812


Contacts
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Contact: Study Director 617-675-1865 clinicaltrials@werewolftx.com

Locations
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United States, Arizona
Honorhealth Not yet recruiting
Scottsdale, Arizona, United States, 85258
Contact: Clinical Trials Nurse Navigation    480-323-1339    clinicaltrials@honorhealth.com   
United States, Georgia
Emory Winship Cancer Institute Not yet recruiting
Atlanta, Georgia, United States, 30322
Contact: Nina Kimball    404-778-8670    nina.cathleen.dobbs.kimball@emory.edu   
United States, Indiana
Indiana University Melvin and Bren Simon Comprehensive Cancer Center Not yet recruiting
Indianapolis, Indiana, United States, 46202
Contact: Anne Younger, RN    317-274-0951    anefoste@iupui.edu   
United States, New York
Westchester Medical Center Not yet recruiting
Hawthorne, New York, United States, 10532
Contact: Zuheir Diab    914-745-6026    zuheir.diab@wmchealth.org   
United States, Texas
NEXT Oncology Recruiting
San Antonio, Texas, United States, 78229
Contact: Cynthia Deleon    210-580-9521    cdeleon@nextoncology.com   
Sponsors and Collaborators
Werewolf Therapeutics, Inc.
Merck Sharp & Dohme LLC
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Responsible Party: Werewolf Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT05479812    
Other Study ID Numbers: WTX-124x2101
First Posted: July 29, 2022    Key Record Dates
Last Update Posted: August 5, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Werewolf Therapeutics, Inc.:
WTX-124
Pembrolizumab
Tumors
Cutaneous Malignant Melanoma
mRCC
Renal Carcinoma
IL-2
Additional relevant MeSH terms:
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Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents