STC-15 as a Part of Combination Therapy With Toripalimab in Selected Advanced Cancers

STORM Therapeutics

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Solid Tumor; Metastatic Non-small Cell Lung Cancer; Metastatic Melanoma; Metastatic Head-and-neck Squamous-cell Carcinoma; Metastatic Endometrial Cancer

Treatments: Combination Product: STC-15 in combination with toripalimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06975293

STC-15-24202

Details and patient eligibility

About

This early phase oncology trial will be conducted at various study centers to investigate the safety, tolerability, and antitumor activity of STC-15 (a METTL3 inhibitor) in combination with toripalimab (anti- programmed cell death 1 [PD-1]) in four different locally advanced unresectable or metastatic tumors such as indications: (1) in combination with toripalimab (anti- programmed cell death 1 [PD-1]) in locally advanced and unresectable or metastatic non-small cell lung cancer (NSCLC), (2) in combination with toripalimab in locally advanced unresectable or metastatic melanoma, (3) in combination with toripalimab in locally advanced unresectable or metastatic endometrial cancers, and (4) in combination with toripalimab in locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC).

This study comprises of 2 parts: a combination dose escalation part (Phase 1b) followed by an assessment of the combination treatment's antitumor activity (Phase 2). This study will be conducted in adult participants with advanced malignancies to characterize the safety, tolerability, PK, and clinical activity of STC-15 in combination with toripalimab.

Enrollment: 188 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Estimated life expectancy ≥ 3 months.
• ECOG performance status 0 or 1.
• Measurable disease according to RECIST v1.1 as assessed by the local site investigator/radiology.
• Documented radiologic assessment of progression on the prior therapy before study entry.
• Have the ability to swallow, retain, and absorb oral medication.

Inclusion Criteria (Expansion):

• NSCLC (when applicable): Participants with AGAs (actionable genetic alterations) must have received targeted therapy unless contraindicated. Participants must not have received more than three previous lines of systemic treatment for unresectable locally advanced or metastatic disease. This must include at least a prior anti-PD-1/L1 alone or in combination with chemotherapy. Participants must have disease progression on prior anti-PD-1/L1.
• HNSCC (when applicable): Participants must have progressed on following prior lines: 2L or 3L recurrent/metastatic disease; regardless of PD-L1 score. Participants must not have received more than three previous lines of systemic treatment for unresectable locally advanced or metastatic disease. This must include at least a prior anti-PD-1/L1 alone or in combination with chemotherapy.
• Endometrial (when applicable): Participants must not have received more than three previous lines of systemic treatment for unresectable locally advanced or metastatic disease. This must include at least a prior anti-PD-1/L1 alone or in combination with chemotherapy. Participants must have disease progression on prior anti-PD-1/L1
• Melanoma (when applicable): Participants must not have received more than three previous lines of systemic treatment for unresectable locally advanced or metastatic disease. This must include at least a prior anti-PD-1/L1 alone or in combination with chemotherapy. Participants must have disease progression on prior anti-PD-1/L1.

Key Exclusion Criteria:

• Pregnant and lactating women.
• Received prior systemic anticancer therapy including investigational agents within 4 weeks prior to first IMP administration.
• Participants who have not recovered from all AEs due to previous therapies to Grade ≤ 1 or baseline, according to NCI-CTCAE v5.0. Exceptions include: alopecia, Grade ≤ 2 neuropathy, and endocrine-related AEs Grade ≤ 2 who are stable on treatment or hormone replacement.
• Major surgery less than 4 weeks prior to the first IMP administration or participants who have not recovered from the side effects of the surgery.
• History of (non-infectious) pneumonitis/interstitial lung disease that required steroids or the presence of ongoing pneumonitis/interstitial lung disease).
• Clinically significant cardiovascular disease or condition.
• Known active CNS metastases and/or leptomeningeal disease.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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188 participants in 5 patient groups

Dose escalation

Experimental group

Description:

Phase 1b 3+3 trial design of dose escalation of STC-15 in combination with toripalimab

Treatment:

Combination Product: STC-15 in combination with toripalimab

Dose expansion NSCLC

Experimental group

Description:

STC-15 in combination with toripalimab (anti-PD-1) in locally advanced and unresectable or metastatic NSCLC

Treatment:

Combination Product: STC-15 in combination with toripalimab

Dose expansion melanoma

Experimental group

Description:

STC-15 in combination with toripalimab in locally advanced unresectable or metastatic melanoma

Treatment:

Combination Product: STC-15 in combination with toripalimab

Dose expansion endometrial cancers

Experimental group

Description:

STC-15 in combination with toripalimab in locally advanced unresectable or metastatic endometrial cancers

Treatment:

Combination Product: STC-15 in combination with toripalimab

Dose expansion HNSCC

Experimental group

Description:

STC-15 in combination with toripalimab in locally advanced or metastatic HNSCC

Treatment:

Combination Product: STC-15 in combination with toripalimab