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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1-2 Dose-escalation and Expansion Study of ST316 in Subjects With Selected Advanced Unresectable and Metastatic Solid Tumors

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

Intervention / Treatment
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* Drug: ST316


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able and willing to sign ICF and comply with the protocol and the restrictions and assessments therein. Male or female ≥18 years of age. ECOG performance status 0-1. Must have a locally advanced or metastatic inoperable tumor as follows: For the dose escalation/regimen exploration phase: CRC, BC, NSCLC, OC, pancreatic adenocarcinoma, melanoma, CC, and synovial sarcoma. For the expansion phase: TNBC, CRC, CC and OC. 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 (unless progressing following irradiation), but a new or progressing lesion in the radiation field is acceptable. Able to provide an archival tumor tissue sample for central lab analysis. This is required for subjects unable to undergo biopsy and must be requested for all others. In the investigator's opinion, the subject may not derive clinical benefit from, or is ineligible for, a particular form of standard therapy on medical grounds, or the subject failed or did not tolerate one or more of other anti-cancer therapies: 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. TNBC must have progressed after prior 1-3 systemic therapies. Patients must have refused or be intolerant to the FDA approved treatments for recurrent TNBC (e.g., iPARP). Patients who are PD-L1 positive should have received, refused or intolerant to pembrolizumab. ii. 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, anti-EGFR targeted agents (as indicated). Patients with MSI-H/dMMR must have received, refused or be intolerant to a check point inhibitor. iii. CC that has recurred or progressed after 1-2 standard treatment regimens. This must include cisplatin and gemcitabine-based therapy (unless a patient refused or was ineligible for treatment). iv. OC that has progressed after 1-3 lines of therapy including a taxane and an anthracycline or intolerant to these agents. Patients must have been treated with, refused, or were ineligible for treatment with bevacizumab to enroll. Patients 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). Evaluable disease per RECIST 1.1 with at least one target lesion. If not menopausal or surgically sterile, willing to practice at least one of the following highly effective methods of birth control for at least a (partner's) menstrual cycle before and for four months after ST316 administration. Exclusion Criteria: Known hypersensitivity to ST316 or any of its excipients. Corrected interval between Q and T wave on ECG (QTc) > 480 msec using Fredericia's formula. 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. 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. For expansion phase only: presence of any other active malignancy requiring systemic therapy other than the disease under study. Concurrent anti-cancer therapy. Known HIV and positive -

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation Phase<br>The dose cohorts will be 0.5, 1, 2, 4, and 8 mg/kg IV once weekly (QW) | Drug: ST316<br>* IV<br>|
| Experimental: Triple Negative Breast Cancer - Expansion phase<br>Triple Negative Breast Cancer Expansion phase n=30 | Drug: ST316<br>* IV<br>|
| Experimental: Colon Rectal Cancer (CRC) Expansion phase<br>Expansion phase n=30 | Drug: ST316<br>* IV<br>|
| Experimental: Cholangiocarcinoma - Expansion phase<br>cholangiocarcinoma Expansion phase n=30 | Drug: ST316<br>* IV<br>|
| Experimental: Ovarian Carcinoma<br>Ovarian Carcinoma - Expansion phase n=30 | Drug: ST316<br>* IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ST316 PK parameter AUCt | Area under the concentration-time curve over the dosing interval | 3 years | 
| ST316 Assessment DOR | DOR is defined for participants achieving a confirmed CR+PR as the time from the initial response of CR+PR per investigator review according to RECIST 1.1 criteria to disease progression or death of any cause, whichever occurs earlier | 3 years | 
| ST316 PK parameter Cmax | Maximum observed serum concentration | 3 years | 
| ST316 PK parameter t1/2 | half life | 3 years | 
| ST316 PK parameter AUC∞ | Area under the concentration-time curve over the dosing interval time from time 0 extrapolated to infinite time | 3 years | 
| ST316 PK parameter tmax. | The time take to reach Maximum observed serum concentration | 3 years | 
| ST316 Assessment Overall survival (OS) | Overall survival (OS) is defined as time from first study treatment to death due to any cause. | 3 Years | 
| ST316 Assessment Progression-free survival (PFS) | Progression-free survival (PFS) is defined as time from first study treatment to a documented disease progression according to RECIST version 1.1, as determined by the investigator, or death due to any cause, whichever occurs earlier. | 3 Years | 
| ST316 Assessment Objective Response Rate (ORR) | ORR defined as percentage of participants with confirmed best overall response of Confirmed complete response (CR) and partial response (PR) per investigator review according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. | 3 Years |