Clinical trial NCT06975293: STC-15 as a Part of Combination Therapy With Toripalimab in Selected Advanced Cancers
Official title: Open-label, Non-randomized, Multi-cohort, Phase 1b/2 Trial Investigating the Safety, Tolerability, and Antitumor Activity of STC-15 (a METTL3 Inhibitor) as a Part of Combination Therapy With Toripalimab in Participants With Selected Advanced Cancers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Metastatic Non-small Cell Lung Cancer
Metastatic Melanoma
Metastatic Endometrial Cancer
Metastatic Head-and-neck Squamous-cell Carcinoma
Solid Tumor
Keywords: STC-15
Toripalimab
PD1
Checkpoint Combination
Lead sponsor: STORM Therapeutics LTD
Sponsor class: INDUSTRY
Collaborators: name: Coherus Biosciences, Inc.
First posted: 2025-05-16
Enrollment: 188
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Safety and tolerability of STC-15 in combination with toripalimab
timeFrame: 6 months
Secondary outcomes:
measure: Anti-tumor activity
timeFrame: 6 months
measure: Maximum observed plasma concentration of STC-15 (Cmax)
timeFrame: 22 days
measure: Recommended Phase 2 Dose
timeFrame: 6 months
measure: Calculated time to reach maximum observed plasma concentration (Tmax)
timeFrame: 22 days
measure: Calculated area under the plasma concentration-time curve of STC-15 (AUC0-t)
timeFrame: 22 days
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: The START Center
state: Texas
city: Fairfax
country: United States
facility: NEXT Oncology
state: Virginia
Study officials:
References: