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

NCT05678998 | Completed Phase 1 Results FDA Drug

• 1 other identifier: WTX-330x2101
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 9

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.

Conditions

Advanced or Metastatic Solid Tumors; Non-Hodgkin Lymphoma

Keywords

WTX-330; Cancer; Immunotherapy; Interleukin-12; IL-12; Checkpoint inhibitor resistance

Outcome Measures

Primary Outcomes (4)

• Incidence of Dose Limiting Toxicities (DLTs)

  A DLT is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, intercurrent illness, or concomitant medications that occurs within the first cycle of treatment with WTX-330 and meets any of the criteria included in the protocol

  4 weeks

• Incidence of Treatment Emergent Adverse Events

  AEs were graded and documented in accordance with NCI-CTCAE version 5.0

  24 months

• Incidence of Changes in Clinical Laboratory Abnormalities

  Change from baseline is provided as baseline grade or "normal/low/high" and worst post-baseline grade.

  24 months

• 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)

  RECIST = Response Evaluation Criteria in Solid Tumors

  24 months

Secondary Outcomes (17)

• Plasma Concentrations of WTX-330 Cycle 1 - C Max

  0, 4, 8, 24, 48, and 168 hours post-dose on Day 1 of Cycle 1

• Plasma Concentrations of WTX-330 Cycle 1 - Time of Maximum Concentration Observation

  0, 4, 8, 24, 48, and 168 hours post-dose on Day 1 of Cycle 1

• Plasma Concentrations of WTX-330 Cycle 1 - Half Life

  0, 4, 8, 24, 48, and 168 hours post-dose on Day 1 of Cycle 1

• Plasma Concentrations of WTX-330 Cycle 1 - AUC

  14 days

• Plasma Concentrations of WTX-330 Cycle 2 - C Max

  0, 4, 8, 24, 48, and 168 hours post-dose on Day 1 of Cycle 2

Study Arms (3)

WTX-330 dose escalation

EXPERIMENTAL

Patients with relapsed/refractory advanced or metastatic solid tumors

Drug: WTX-330

WTX-330 dose expansion in patients for whom CPI therapy is indicated (Arm A)

EXPERIMENTAL

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

WTX-330 dose expansion in patients for whom CPI therapy is not indicated (Arm B)

EXPERIMENTAL

WTX-330 dose expansion in patients with tumor types for which a CPI is not indicated/ approved

Drug: WTX-330

Interventions

WTX-330 DRUG

Investigation Product

WTX-330 dose escalation; WTX-330 dose expansion in patients for whom CPI therapy is indicated (Arm A); WTX-330 dose expansion in patients for whom CPI therapy is not indicated (Arm B)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• 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.
• 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.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• At least one measurable lesion per RECIST 1.1 or an evaluable lesion per Lugano classification (for lymphoma).
• Agrees to undergo a pre-treatment and on-treatment biopsy of a primary or metastatic solid tumor or lymphoma lesion.
• HIV-infected patients must be on antiretroviral therapy and have well-controlled disease.
• Adequate organ and bone marrow function.
• 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.
• Additional criteria may apply.

You may not qualify if:

• 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.
• Received prior treatment with IL-12, including by intratumoral injection.
• Patients with primary CNS malignancies.
• 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.
• Significant cardiovascular disease.
• Significant electrocardiogram (ECG) abnormalities
• Active autoimmune disease requiring systemic treatment in the past 2 years.
• Diagnosis of immunodeficiency, on immunosuppressive therapy, or receiving chronic systemic or enteric steroid therapy (dose \> 10 mg/day of prednisone or equivalent).
• Prior receipt of an allogeneic stem cell transplant or allogeneic CAR-T cell therapy.
• 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 anticancer herbal remedy) within 5 half-lives or 4 weeks (whichever is shorter) prior to the first dose of study drug.
• 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.
• 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.
• Use of sensitive substrates of major CYP450 isozymes.
• 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.

Sponsors & Collaborators

• Werewolf Therapeutics, Inc.: lead

Study Sites (9)

HonorHealth

Scottsdale, Arizona, 85258, United States

Location

Emory Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Mass General Hospital

Boston, Massachusetts, 02114, United States

Location

Facility Name: Roswell Park Comprehensive Cancer Care

Buffalo, New York, 14203, United States

Location

Providence Cancer Institute Franz Clinic

Portland, Oregon, 97213, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Neoplasms

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Werewolf Study Director
• Organization: Werewolf Therapeutics

clinicaltrials@werewolftx.com

617-675-1865

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2022
• First Posted: January 10, 2023
• Study Start: December 6, 2022
• Primary Completion: December 23, 2024
• Study Completion: February 5, 2025
• Last Updated: January 6, 2026
• Results First Posted: January 6, 2026

Record last verified: 2025-12

Locations

US (9)