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

• ClinicalTrials.gov Identifier: NCT05678998
• Recruitment Status: Recruiting
• First Posted: January 10, 2023
• Last Update Posted: January 10, 2023
• Sponsor: Werewolf Therapeutics, Inc.
• Information provided by (Responsible Party): Werewolf Therapeutics, Inc.

Study Description

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.

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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 ]

Eligibility Criteria

• 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

Contacts and Locations

Contacts

Contact: Study Director; 617-952-0555; clinicaltrials@werewolftx.com

Locations

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.

More Information

• Responsible Party: Werewolf Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT05678998
• Other Study ID Numbers: WTX-330x2101
• First Posted: January 10, 2023
• Last Update Posted: January 10, 2023
• Last Verified: January 2023

• 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:

Lymphoma; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases