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

Sponsor

Werewolf Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05479812

Collaborator

Merck Sharp & Dohme LLC (Industry)

150

Enrollment

Locations

Arms

38.4

Anticipated Duration (Months)

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

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 solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Solid Tumor Advanced Solid Tumor	Drug: WTX-124 Drug: Pembrolizumab	Phase 1

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 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

May 20, 2022

Anticipated Primary Completion Date :

Jul 1, 2025

Anticipated Study Completion Date :

Jul 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: WTX-124 monotherapy dose escalation	Drug: WTX-124 Investigation Product Monotherapy
Experimental: WTX-124 monotherapy dose expansion in advanced or metastatic cutaneous malignant melanoma	Drug: WTX-124 Investigation Product Monotherapy
Experimental: WTX-124 monotherapy dose expansion in advanced or metastatic RCC	Drug: WTX-124 Investigation Product Monotherapy
Experimental: WTX-124 in combination with pembrolizumab dose escalation	Drug: WTX-124 Investigation Product Monotherapy Drug: Pembrolizumab Investigation Product in combination with approved therapy
Experimental: WTX-124 in combo with pembro dose expansion in advanced/metastatic cutaneous malignant melanoma	Drug: WTX-124 Investigation Product Monotherapy Drug: Pembrolizumab Investigation Product in combination with approved therapy
Experimental: WTX-124 in combination with pembrolizumab dose expansion in advanced or metastatic RCC	Drug: WTX-124 Investigation Product Monotherapy Drug: Pembrolizumab Investigation Product in combination with approved therapy

Outcome Measures

Primary Outcome Measures

Incidence of Dose Limiting Toxicities (DLTs) in monotherapy and combination therapy [4 weeks]
Incidence of treatment emergent adverse events in monotherapy and combination therapy [24 months]
Incidence of changes in clinical laboratory abnormalities in monotherapy and combination therapy [24 months]
Investigator-assessed objective response rate (ORR) per RECIST 1.1 and iORR by iRECIST in monotherapy and combination therapy [24 months]

Secondary Outcome Measures

Plasma concentrations of WTX-124 and free IL-2 [24 months]
Investigator-assessed objective response rate (ORR) per RECIST 1.1 and iORR by iRECIST in monotherapy and combination therapy [24 months]
Changes in circulating immune cell populations in response to monotherapy and combination therapy [24 months]
Changes in soluble cytokines in response to monotherapy and combination therapy [24 months]
Changes in tumor immune profile in response to monotherapy and combination therapy [24 months]
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]
Antidrug antibody (ADA) occurrence [24 months]
Duration of response [24 months]
Progression free survival [24 months]
Overall survival [36 months]
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]
To assess tumor biopsies for potential biomarkers of target engagement and immune pathway activation [24 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Each patient must meet all the following criteria to participate in the study:

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;
≥18 years of age;
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
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);
Agrees to undergo a pre-treatment and on-treatment biopsy of a primary or metastatic solid tumor lesion;
Has adequate organ and bone marrow function:
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;
Additional criteria may apply

Exclusion Criteria:

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;
Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease;
Have received prior IL-2-directed therapy;
Have had an allogeneic tissue/solid organ transplant;
Have known symptomatic brain metastases requiring steroids;
Have significant cardiovascular disease;
Have an active autoimmune disease that required systemic treatment in the past 2 years;
Diagnosis of immunodeficiency, is on immunosuppressive therapy, or is receiving chronic systemic or enteric steroid therapy
Major surgery (excluding placement of vascular access) within 2 weeks prior to the first dose of study drug;
Investigational agent or anticancer therapy within 5 half-lives or 4 weeks (whichever is shorter) prior to the first dose of study drug;
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;
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;
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.
Active, uncontrolled systemic bacterial, viral, or fungal infection;
HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease;
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;
Active infection as determined by hepatitis C virus (HCV) antibody or HCV RNA by qPCR testing;
Pregnant or lactating;
History of hypersensitivity to any of the study drug components;
Additional criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Honorhealth	Scottsdale	Arizona	United States	85258
2	Emory Winship Cancer Institute	Atlanta	Georgia	United States	30322
3	Indiana University Melvin and Bren Simon Comprehensive Cancer Center	Indianapolis	Indiana	United States	46202
4	Westchester Medical Center	Hawthorne	New York	United States	10532
5	NEXT Oncology	San Antonio	Texas	United States	78229