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Testing WTX-124 alone and with pembrolizumab in patients with advanced solid tumors

A Multicenter Phase I/Ib Dose Escalation and Expansion Study of WTX-124 as Monotherapy and in Combination With Pembrolizumab in Patients With Selected Advanced or Metastatic Solid Tumors

Phase 1 Interventional Werewolf Therapeutics, Inc. · NCT05479812

This study is testing a new treatment called WTX-124, both alone and with another drug called pembrolizumab, to see if it can help people with advanced solid tumors feel better.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment150 (estimated)
Ages18 Years and up
SexAll
SponsorWerewolf Therapeutics, Inc. Industry-sponsored
Drugs / interventionsimmunotherapy, radiation, pembrolizumab
Locations11 sites (Scottsdale, Arizona and 10 other locations)
Trial IDNCT05479812 on ClinicalTrials.gov

What this trial studies

This Phase I, open-label, multicenter study aims to evaluate the safety, tolerability, and preliminary efficacy of WTX-124, a conditionally-activated IL-2 prodrug, in patients with advanced or metastatic solid tumors. The study consists of two parts: the first part focuses on dose escalation of WTX-124 both as a standalone treatment and in combination with pembrolizumab. The second part involves dose expansion across six arms, targeting patients with advanced or metastatic cutaneous malignant melanoma and renal cell carcinoma. The goal is to determine the optimal dosing and effectiveness of these treatments in this patient population.

Who should consider this trial

Good fit: Ideal candidates include patients with relapsed or refractory advanced or metastatic solid tumors who have progressed on or are intolerant to standard therapies.

Not a fit: Patients with early-stage tumors or those who have not yet received standard therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with advanced solid tumors who have limited therapeutic alternatives.

How similar studies have performed: Other studies have shown promise with similar immunotherapy approaches, but this specific combination is novel.

Eligibility criteria

Show full inclusion / exclusion 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 1 prior line of 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.

Where this trial is running

Scottsdale, Arizona and 10 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Metastatic Solid TumorAdvanced Solid TumorWTX-124pembrolizumabTumorsCutaneous Malignant MelanomamRCCRenal Carcinoma
Last reviewed 2026-06-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.