We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

WTX-330 in Patients With Advanced or Metastatic Solid Tumors or Non-Hodgkin Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05678998
Recruitment Status : Recruiting
First Posted : January 10, 2023
Last Update Posted : January 10, 2023
Sponsor:
Information provided by (Responsible Party):
Werewolf Therapeutics, Inc.

Brief Summary:
A first-in-human, Phase 1, open-label, multicenter study of WTX-330 administered as a monotherapy to patients with advanced or metastatic solid tumors or non-Hodgkin lymphoma.

Condition or disease Intervention/treatment Phase
Advanced or Metastatic Solid Tumors Non-Hodgkin Lymphoma Drug: WTX-330 Phase 1

Detailed Description:
This is a first-in-human, Phase 1, open-label, multicenter study to evaluate the safety, tolerability and preliminary efficacy of WTX-330, a conditionally-activated IL-12 prodrug, when administered as a monotherapy to patients with advanced or metastatic solid tumors or non-Hodgkin lymphoma. Dose escalation will be conducted in patients with advanced and/or metastatic solid tumors who are refractory to all standard of care therapies. Dose expansion will be conducted in two arms: Arm A will enroll patients with indications for which a checkpoint inhibitor (CPI) is indicated/approved who demonstrate primary or secondary resistance to an anti-PD(L)1 treatment regimen, and Arm B will enroll patients with tumor types for which CPI therapy is not indicated/approved.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 (First-In-Human [FIH]), Multi-Site, Dose Escalation and Expansion Study of WTX-330 in Adult Patients With Advanced or Metastatic Solid Tumors or Lymphoma
Actual Study Start Date : December 6, 2022
Estimated Primary Completion Date : November 2023
Estimated Study Completion Date : November 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: WTX-330 dose escalation
Patients with relapsed/refractory advanced or metastatic solid tumors
Drug: WTX-330
Investigation Product

Experimental: WTX-330 dose expansion in patients for whom CPI therapy is indicated (Arm A)
WTX-330 dose expansion in patients with tumor types for which a CPI is indicated/approved who demonstrate primary or secondary resistance to an anti-PD(L)1-based regimen
Drug: WTX-330
Investigation Product

Experimental: WTX-330 dose expansion in patients for whom CPI therapy is not indicated (Arm B)
WTX-330 dose expansion in patients with tumor types for which a CPI is not indicated/ approved
Drug: WTX-330
Investigation Product




Primary Outcome Measures :
  1. Incidence of Dose Limiting Toxicities (DLTs) [ Time Frame: 4 weeks ]
  2. Incidence of treatment emergent adverse events [ Time Frame: 24 months ]
  3. Incidence of changes in clinical laboratory abnormalities [ Time Frame: 24 months ]
  4. Investigator-assessed objective response rate (ORR) by RECIST 1.1 and immune ORR by iRECIST (for solid tumors) or response by Lugano criteria (for lymphomas) [ Time Frame: 24 months ]

Secondary Outcome Measures :
  1. Plasma concentrations of WTX-330 and free IL-12 [ Time Frame: 24 months ]
  2. Changes in circulating immune cell populations [ Time Frame: 24 months ]
  3. Changes in soluble cytokines including IL-2, IL-4, IL-6, IL-10, IFN-γ and IP-10 [ Time Frame: 24 months ]
  4. Changes in tumor immune cell profile by immunohistochemistry (IHC) [ Time Frame: 24 months ]
  5. Investigator-assessed ORR by RECIST 1.1 and immune ORR by iRECIST (for solid tumors) or response by Lugano criteria (for lymphomas) in patients who have progressed on CPIs or who have tumor indications for which CPIs are not approved [ Time Frame: 24 months ]
  6. Antidrug antibody (ADA) occurrence [ Time Frame: 24 months ]
  7. Duration of response [ Time Frame: 24 months ]
  8. Progression free survival [ Time Frame: 24 months ]
  9. Overall survival [ Time Frame: 36 months ]
  10. Identification of potential biomarkers of target engagement and immune pathway activation in tumor biopsies [ Time Frame: 24 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  1. Age ≥ 18 years.
  2. Dose Escalation: A diagnosis of a relapsed/refractory advanced or metastatic solid tumor for which the patient has progressed on or is intolerant of standard therapy, or for whom no standard therapy with proven benefit exists.
  3. Dose Expansion: A diagnosis of a relapsed/refractory advanced or metastatic malignancy for which the patient has progressed on or is intolerant of standard therapy, or for whom no standard therapy with proven benefit exists. For Arm A, patients must have a tumor type for which a CPI is indicated/approved and demonstrate primary or secondary resistance to a standard of care anti-PD(L)1-based treatment regimen. For Arm B, patients must have a solid tumor type for which a CPI is not indicated/approved or non-Hodgkin lymphoma.
  4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  5. At least one measurable lesion per RECIST 1.1 or an evaluable lesion per Lugano classification (for lymphoma).
  6. Agrees to undergo a pre-treatment and on-treatment biopsy of a primary or metastatic solid tumor or lymphoma lesion.
  7. HIV-infected patients must be on antiretroviral therapy and have well-controlled disease.
  8. Adequate organ and bone marrow function.
  9. Willingness of men and women of reproductive potential to use highly effective birth control for the duration of treatment and for 4 months following the last dose of study drug.
  10. Additional criteria may apply.

Exclusion Criteria:

  1. A history of another active malignancy (i.e., 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, present 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. Received prior treatment with IL-12, including by intratumoral injection.
  3. Patients with primary CNS malignancies.
  4. Presence of CNS metastases that are symptomatic and/or require local CNS directed therapy (such as XRT or surgery) or increasing doses of corticosteroids within 2 weeks prior to the first dose of study drug. Patients with treated brain metastases should be neurologically stable and receiving ≤ 10 mg per day of prednisone or equivalent prior to study entry.
  5. Significant cardiovascular disease.
  6. Significant electrocardiogram (ECG) abnormalities
  7. Active autoimmune disease requiring systemic treatment in the past 2 years.
  8. Diagnosis of immunodeficiency, on immunosuppressive therapy, or receiving chronic systemic or enteric steroid therapy (dose > 10 mg/day of prednisone or equivalent).
  9. Prior receipt of an allogeneic stem cell transplant or allogeneic CAR-T cell therapy.
  10. Major surgery (excluding placement of vascular access) within 2 weeks prior to the first dose of study drug.
  11. Investigational agent or anticancer therapy (including chemotherapy, biologic therapy, immunotherapy, anticancer Chinese medicine, or anticancer herbal remedy) within 5 half-lives or 4 weeks (whichever is shorter) prior to the first dose of study drug.
  12. Radiotherapy within 2 weeks of the start of study treatment. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease.
  13. 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 platinum therapy-related neuropathy.
  14. Use of sensitive substrates of major CYP450 isozymes.
  15. Any illness, medical condition, organ system dysfunction, or social situation (including mental illness or substance abuse), that may interfere with a patient's ability to sign the ICF, adversely affect the patient's ability to cooperate and participate in the study, or compromise interpretation of study results.
  16. Received a live vaccine within 30 days of the first dose of study drug.
  17. Active, uncontrolled systemic bacterial, viral, or fungal infection.
  18. HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.
  19. Active infection with hepatitis B as determined by hepatitis B surface antigen and hepatitis B core antibody, or hepatitis B virus deoxyribonucleic acid (DNA) by quantitative polymerase chain reaction (qPCR) testing.
  20. Active infection with hepatitis C as determined by hepatitis C virus (HCV) antibody or HCV RNA by qPCR testing.
  21. Pregnant or lactating.
  22. History of hypersensitivity to any of the study drug components.
  23. 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): NCT05678998


Contacts
Layout table for location contacts
Contact: Study Director 617-952-0555 clinicaltrials@werewolftx.com

Locations
Layout table for location information
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.
Layout table for additonal information
Responsible Party: Werewolf Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT05678998    
Other Study ID Numbers: WTX-330x2101
First Posted: January 10, 2023    Key Record Dates
Last Update Posted: January 10, 2023
Last Verified: January 2023

Layout table for additional information
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-330
Cancer
Immunotherapy
Interleukin-12
IL-12
Checkpoint inhibitor resistance
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases