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

Advanced Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05479812
• Other study ID #: WTX-124x2101
• Secondary ID: MK-3475-D17KEYNO
• Status: Recruiting
• Phase: Phase 1
• Start date: May 20, 2022
• Est. completion date: July 31, 2025

Study information

• Verified date: March 2024
• Source: Werewolf Therapeutics, Inc.
• Contact: Study Director
• Phone: 617-675-1865
• Email: clinicaltrials[@]werewolftx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 solid tumors.

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 comprised of four 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: July 31, 2025
• Est. primary completion date: July 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. =18 years of age;

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

4. 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);

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

6. Has adequate organ and bone marrow function:

7. 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;

8. 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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Metastatic Solid Tumor
• Neoplasms

Intervention

Drug:
• WTX-124
Investigation Product Monotherapy
• pembrolizumab
Investigation Product in combination with approved therapy

Locations

Country	Name	City	State
United States	Emory Winship Cancer Institute	Atlanta	Georgia
United States	Roswell Park Comprehensive Cancer Care	Buffalo	New York
United States	Northwestern University	Chicago	Illinois
United States	Westchester Medical Center	Hawthorne	New York
United States	Indiana University Melvin and Bren Simon Comprehensive Cancer Center	Indianapolis	Indiana
United States	Providence Cancer Institute Franz Clinic	Portland	Oregon
United States	NEXT Oncology	San Antonio	Texas
United States	HonorHealth	Scottsdale	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Werewolf Therapeutics, Inc.	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Dose Limiting Toxicities (DLTs) in monotherapy and combination therapy		4 weeks
Primary	Incidence of treatment emergent adverse events in monotherapy and combination therapy		24 months
Primary	Incidence of changes in clinical laboratory abnormalities in monotherapy and combination therapy		24 months
Primary	Investigator-assessed objective response rate (ORR) per RECIST 1.1 and iORR by iRECIST in monotherapy and combination therapy		24 months
Secondary	Plasma concentrations of WTX-124 and free IL-2		24 months
Secondary	Investigator-assessed objective response rate (ORR) per RECIST 1.1 and iORR by iRECIST in monotherapy and combination therapy		24 months
Secondary	Changes in circulating immune cell populations in response to monotherapy and combination therapy		24 months
Secondary	Changes in soluble cytokines in response to monotherapy and combination therapy		24 months
Secondary	Changes in tumor immune profile in response to monotherapy and combination therapy		24 months
Secondary	Investigator-assessed objective response rate (ORR) per RECIST 1.1 and iORR by iRECIST in monotherapy and combination therapy (in advanced or metastatic renal cell carcinoma and advanced or metastatic cutaneous malignant melanoma)		24 months
Secondary	Antidrug antibody (ADA) occurrence		24 months
Secondary	Duration of response		24 months
Secondary	Progression free survival		24 months
Secondary	Overall survival		36 months
Secondary	To investigate immunological biomarkers in peripheral blood and tumor that may correlate with the treatment outcome of WTX-124 as monotherapy or in combination with pembrolizumab		24 months
Secondary	To assess tumor biopsies for potential biomarkers of target engagement and immune pathway activation		24 months