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

NCT ID: NCT05479812

Last Updated: 2025-12-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-20
• Study Completion Date: 2026-07-31

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 or metastatic solid tumors.

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 dose expansion and is comprised of six 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.

Conditions

Metastatic Solid Tumor; Advanced Solid Tumor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm E: WTX-124 with pembro dose expansion. Advanced or metastatic cutaneous melanoma.

Arm E: WTX-124 in combination with pembrolizumab dose expansion. Patients with advanced or metastatic cutaneous melanoma.

Group Type: EXPERIMENTAL

WTX-124

Intervention Type: DRUG

Investigation Product Monotherapy

pembrolizumab

Intervention Type: DRUG

Investigation Product in combination with approved therapy

Arm F: WTX-124 in combination with pembro dose expansion. Advanced/metastatic PD-L1-positive NSCL

Arm F: WTX-124 in combination with pembrolizumab dose expansion. Patients with advanced or metastatic PD-L1-positive NSCLC lines.

Group Type: EXPERIMENTAL

WTX-124

Intervention Type: DRUG

Investigation Product Monotherapy

pembrolizumab

Intervention Type: DRUG

Investigation Product in combination with approved therapy

WTX-124 monotherapy dose escalation

WTX-124 monotherapy dose escalation

Group Type: EXPERIMENTAL

WTX-124

Intervention Type: DRUG

Investigation Product Monotherapy

WTX-124 in combination with pembro dose escalation

WTX-124 in combination with pembrolizumab (pembro) dose escalation

Group Type: EXPERIMENTAL

WTX-124

Intervention Type: DRUG

Investigation Product Monotherapy

pembrolizumab

Intervention Type: DRUG

Investigation Product in combination with approved therapy

Arm A: WTX-124 monotherapy dose expansion. Patients with advanced or metastatic RCC.

Arm A: WTX-124 monotherapy dose expansion. Patients with advanced or metastatic RCC.

Group Type: EXPERIMENTAL

WTX-124

Intervention Type: DRUG

Investigation Product Monotherapy

Arm B: WTX-124 monotherapy dose expansion. Advanced or metastatic cutaneous malignant melanoma.

Arm B: WTX-124 monotherapy dose expansion. Patients with advanced or metastatic cutaneous malignant melanoma.

Group Type: EXPERIMENTAL

WTX-124

Intervention Type: DRUG

Investigation Product Monotherapy

Arm C: WTX-124 monotherapy dose expansion. Patients with advanced or metastatic cSCC.

Arm C: WTX-124 monotherapy dose expansion. Patients with advanced or metastatic cSCC.

Group Type: EXPERIMENTAL

WTX-124

Intervention Type: DRUG

Investigation Product Monotherapy

Arm D: WTX-124 in combination with pembro dose expansion. Advanced or metastatic RCC.

Arm D: WTX-124 in combination with pembrolizumab dose expansion. Patients with advanced or metastatic RCC.

Group Type: EXPERIMENTAL

WTX-124

Intervention Type: DRUG

Investigation Product Monotherapy

pembrolizumab

Intervention Type: DRUG

Investigation Product in combination with approved therapy

Interventions

WTX-124

Investigation Product Monotherapy

Intervention Type: DRUG

pembrolizumab

Investigation Product in combination with approved therapy

Intervention Type: DRUG

Other Intervention Names

KEYTRUDA®

Eligibility 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. 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.

Monotherapy Dose Expansion:

• Arm A: Patients with relapsed advanced or metastatic RCC who have received no more than 4 prior lines of therapy in the advanced or metastatic setting
• Arm B: Patients with relapsed advanced or metastatic cutaneous malignant melanoma who have received no more than 2 prior lines of therapy for BRAF V600 wild type and no more than 3 prior lines of therapy for BRAF V600 mutant melanoma.
• Arm C: Patients with relapsed advanced or metastatic cSCC who have received no more than 2 prior lines of systemic therapy

Combination Dose Expansion:

1. Arm D: Patients with RCC who have received no more than 3 prior lines of therapy

2. Arm E: Patients with cutaneous melanoma who may be naïve to all prior therapy for advanced or metastatic disease. For BRAF wild type melanoma, patients should have received no more than 2 prior lines of therapy. For BRAF V600 mutant disease, patients should have received no more than 3 prior lines of therapy.

3. Arm F: Patients with PD-L1-positive NSCLC who have received no more than 3 prior lines;

3. ≥18 years of age;

4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;

5. 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);

6. Agrees to undergo a pre-treatment and on-treatment biopsy of a primary or metastatic solid tumor lesion;

7. Has adequate organ and bone marrow function;

8. 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;

9. 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Werewolf Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

HonorHealth

Scottsdale, Arizona, United States

Site Status: RECRUITING

Moffitt Cancer Center

Tampa, Florida, United States

Site Status: RECRUITING

Emory Winship Cancer Institute

Atlanta, Georgia, United States

Site Status: RECRUITING

Northwestern University

Chicago, Illinois, United States

Site Status: RECRUITING

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, United States

Site Status: RECRUITING

Minnesota Oncology Hematology, P.A.

Maple Grove, Minnesota, United States

Site Status: TERMINATED

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status: RECRUITING

Roswell Park Comprehensive Cancer Care

Buffalo, New York, United States

Site Status: RECRUITING

Westchester Medical Center

Hawthorne, New York, United States

Site Status: TERMINATED

Providence Cancer Institute Franz Clinic

Portland, Oregon, United States

Site Status: TERMINATED

Texas Oncology - Austin Midtown

Austin, Texas, United States

Site Status: TERMINATED

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status: RECRUITING

NEXT Oncology

Houston, Texas, United States

Site Status: RECRUITING

NEXT Oncology

San Antonio, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Study Director

Role: CONTACT

clinicaltrials@werewolftx.com

617-675-1865

Facility Contacts

Clinical Trials Nurse Navigation

Role: primary

clinicaltrials@honorhealth.com

480-323-1339

Malik Hall

Role: primary

Malik.Hall@Moffitt.org

813-745-5170

Nina Kimball

Role: primary

nina.cathleen.dobbs.kimball@emory.edu

404-778-8670

Study Coordinator

Role: primary

cancertrials@northwestern.edu

312-695-1301

Anne Younger, RN

Role: primary

anefoste@iupui.edu

317-274-0951

Oncology Clinical Research Referral Office

Role: primary

oncologyresearchreferral@hmhn.org

551-996-1777

Kim Benczkowski

Role: primary

askroswell@roswellpark.org

1-800-767-9355

Leta Ko

Role: primary

Leta.ko@utsouthwestern.edu

214-648-2279

Emma Morales

Role: primary

emorales@nextoncology.com

832-384-7912

Cynthia Deleon

Role: primary

cdeleon@nextoncology.com

210-580-9521

Other Identifiers

MK-3475-D17

Identifier Type: OTHER

Identifier Source: secondary_id

KEYNOTE-D17

Identifier Type: OTHER

Identifier Source: secondary_id

WTX-124x2101

Identifier Type: -

Identifier Source: org_study_id