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

What this study involves

The registry does not currently label this study as recruiting. Ask about its status before planning a screening visit.

Study type

Interventional

Phase

Phase 1

Age range

18 years - Not specified

Sex eligible

All sexes

Healthy volunteers

Not accepted

Participants

156 Actual

These are starting points, not an eligibility decision. The research team must review the full requirements.

About the research

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.

Who may be able to participate?

The list below is the sponsor’s full registry wording. It can include conditions, prior treatment, test results and other requirements. A match in search does not mean you qualify.

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.

Treatment, groups and participation

The registry may describe treatments and study duration without a complete visit calendar. Ask the study team for the exact schedule, procedures, risks, costs and alternatives. Keep your usual care plan unless your treating clinician tells you otherwise.

Assignment

Not randomized

Masking

No masking

What researchers are measuring

Outcome measures describe what is being studied. They are not proof that a treatment works.

Primary measures

Secondary measures

Research locations (14)

The overall study status and a local site’s status can differ. Confirm that location’s availability before traveling.

14 locations

Study team and timeline

Lead sponsor

Werewolf Therapeutics, Inc.

Study start

Aug 15, 2022 Actual

Primary completion

Apr 22, 2026 Actual

Study completion

Apr 22, 2026 Actual

First posted

Jul 29, 2022 Actual

Last updated

Nov 10, 2026 Actual

Official study contacts

No central contact is listed. Check the locations and the official record.