A Phase 1-2 of ST316 With Selected Advanced Unresectable and Metastatic Solid Tumors

Sapience Therapeutics

Status and phase: Enrolling; Phase 1

Conditions: Metastatic Skin Cancer; Melanoma Stage IV; TNBC - Triple-Negative Breast Cancer; Colon Cancer; NSCLC, Metastatic; Cholangiocarcinoma; Ovarian Cancer; Metastatic Colon Cancer; Melanoma Recurrent; Breast Cancer Metastatic; Hepatocellular Carcinoma; Metastatic Melanoma; Synovial Sarcoma; Triple Negative Breast Cancer; Pancreatic Cancer

Treatments: Drug: Fruquintinib; Drug: FOLFIRI regimen & bevacizumab; Drug: ST316

Study type: Interventional

Funder types: Industry

Identifiers

NCT05848739

ST316-101

Details and patient eligibility

About

This is an open-label, two-part, phase 1-2 study designed to determine the safety, tolerability, PK, pharmacodynamics (PD), and proof-of-concept efficacy of ST316 administered IV in subjects with selected advanced solid tumors likely to harbor abnormalities of the WNT/β-catenin signaling pathway. The study consists of two phases: a phase 1 dose escalation/regimen exploration phase and a phase 2 expansion phase.

Enrollment: 115 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Able and willing to sign ICF and comply with the protocol and the restrictions and assessments therein.

2. Male or female ≥18 years of age.

3. ECOG performance status 0-1.

4. Must have a locally advanced or metastatic inoperable tumor as follows:

   1. For the dose escalation/regimen exploration phase: CRC, BC, NSCLC, OC, pancreatic adenocarcinoma, melanoma, CC, and synovial sarcoma.
   2. For the expansion phase: CRC

5. Agrees to provide a newly obtained biopsy of an accessible lesion (if they can be biopsied based on the Investigator's assessment) prior to the start of study treatment, and to repeat biopsy once during study treatment. Tissue obtained for the biopsy must not be previously irradiated, but a new or progressing lesion in the radiation field is acceptable. Subjects without accessible lesion for biopsy must be able to provide an archival tumor tissue sample for central lab analysis.

   a. For the dose escalation/regimen exploration phase: i. Refractory, intolerant, or refused all available standard-of-care therapies ii. Up to 3 previous lines of systemic anticancer therapies for metastatic disease are allowed.

iii. Patients with TNBC or OC with known BRCA mutations must have been previously treated with or intolerant to FDA approved treatments prior to enrolling in this study (e.g. iPARP).

iv. Patients with OC must have been treated with, refused, or were ineligible for treatment with bevacizumab to enroll.

v. Patients with CRC tumors that are MSI-H/dMMR must have received, refused or be intolerant to a check point inhibitor.

b. For the expansion phase: i. For all cohorts: Subjects with MSI-H/dMMR must have received, refused or be intolerant to a CPI.

ii. Cohort 1 monotherapy: CRC that has progressed after or on treatment with all of the following, alone or in combination, comprising a maximum of 4 prior lines of therapy for their advanced/metastatic disease: oxaliplatin, irinotecan, fluoropyrimidines, anti-vascular-endothelial growth factor (VEGF), anti-epidermal growth factor receptor (EGFR) targeted agents (as indicated).

iii. Cohort 2: Combination with standard of care (SOC) FOLFIRI + bevacizumab: CRC that has progressed after or on treatment with all of the following, alone or in combination, comprising a maximum of 1 prior line of therapy for their advanced/metastatic disease: oxaliplatin, irinotecan, fluoropyrimidines, anti-VEGF. Subjects with RAS wild-type must have been treated with an anti-EGFR targeted agent during the first line of treatment.

iv. Cohort 3: Combination with fruquintinib: CRC that has progressed after or on treatment with all of the following, alone or in combination, comprising a maximum of 3 prior lines of therapy for their advanced/metastatic disease: oxaliplatin, irinotecan, fluoropyrimidines, anti-VEGF, regorafenib or lonsurf. Subjects with RAS wild-type must have been treated with an anti-EGFR targeted agent during the first line of treatment.

Exclusion criteria

1. Known hypersensitivity to ST316 or any of its excipients.
2. Corrected interval between Q and T wave on ECG (QTc) > 480 msec using Fredericia's formula.
3. Symptomatic ascites or pleural effusion. A subject who is clinically stable for 4 weeks following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
4. Known active CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are clinically stable for at least 2 weeks prior to study entry and have no evidence of new or enlarging brain metastases. Subjects with treated brain metastases must also follow the steroid exclusion criterion (#9) listed below.
5. For expansion phase only: presence of any other active malignancy requiring systemic therapy other than the disease under study.
6. Concurrent anti-cancer therapy.
7. Known HIV and positive -

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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115 participants in 4 patient groups

Dose Escalation Phase

Experimental group

Description:

The dose cohorts will be 0.5, 1, 2, 4, 8 \& 12 mg/kg IV once weekly (QW)

Treatment:

Drug: ST316

ST316 Monotherapy Colon Rectal Cancer (CRC) Expansion phase

Experimental group

Description:

ST316 Monotherapy Colon Rectal Cancer (CRC) Expansion phase n=30

Treatment:

Drug: ST316

ST316 & FOLFIRI/Bevacizumab Combination Colon Rectal Cancer (CRC) Expansion phase

Experimental group

Description:

ST316 \& FOLFIRI/Bevacizumab Combination Colon Rectal Cancer (CRC) Expansion phase Expansion phase n=30

Treatment:

Drug: FOLFIRI regimen & bevacizumab

Drug: ST316

ST316 & Fruquintinib Combination CRC Expansion phase

Experimental group

Description:

ST316 \& Fruquintinib Combination CRC Expansion phase n=30

Treatment:

Drug: ST316

Drug: Fruquintinib