Advanced Solid Tumor
Conditions
Keywords
Intravenous, Non Small Cell Lung Cancer, Melanoma, Advanced Solid Tumors, mRNA
Brief summary
Phase 1/2, Open-label, Multi-center, First-in-human Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of STX-003 Delivered by Intravenous Injection in Patients with Advanced Solid Tumors as a Monotherapy or in Combination with Pembrolizumab.
Detailed description
This open-label, Phase 1/2, first-in-human (FIH), multiple ascending dose and dose expansion study involves STX-003 administration, alone or in combination with pembrolizumab, to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity in patients with advanced cancers. (Update after review)
Interventions
BIOLOGICALSTX-003
STX-003 is a LNP formulated self-replicating mRNA encoding the therapeutic payload human IL-12 (hIL-12) with miRNA target sites to sense specific endogenous miRs.
BIOLOGICALKEYTRUDA®
Pembrolizumab (Keytruda USPI 2026) is a marketed PD-1 blocking humanized monoclonal IgG4 kappa antibody.
Sponsors
Strand Therapeutics Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Inclusion Criteria (Phase 1 and Phase 2) 1. Mentally competent and able to understand and sign the ICF. 2. Tumor type for which there is an FDA-approved anti-PD-1/L1 antibody therapy, specifically including biomarker labeled subsets (i.e. PD-L1+) as well as anatomical subsets in some disease (cutaneous melanoma is eligible whereas acral, mucosal and uveal are not; Phase 1) and advanced cutaneous melanoma or PD-L1+ NSCLC. 3. Histologically or cytologically documented, locally advanced, or metastatic solid tumor. 4. At least one measurable lesion per RECIST v1.1 criteria. 5. The patient lacks a curative therapy or has progressive disease despite, or refused, standard therapy. 6. ECOG performance status of 0 or 1. 7. Life expectancy of ≥ 12 weeks per the Investigator. 8. ≥ 18 years of age at the time of informed consent. 9. Body weight ≥ 40 kg. 10. WOCBP and males with female partners of child-bearing potential must agree to use adequate birth control throughout their participation and for 3 months following the last dose of STX-003. 11. Willing and able to comply with protocol required assessments. Hematology: * ANC ≥ 1,000 cells/mm3. * Platelet count ≥ 75,000 cells/mm3. * Hemoglobin ≥ 8.0 g/dL. * Renal: Serum creatinine \< 1.5 × ULN or creatinine clearance ≥ 40 mL/min based on the Cockcroft-Gault glomerular filtration rate estimation Coagulation: * PT/INR or PT must be ≤ 1.5 × ULN. * aPTT ≤ 1.5 × ULN unless undergoing anticoagulation therapy. • Liver: * Albumin ≥ 3.5 g/dL or within the normal range of the local reference laboratory. * AST and ALT \< 2 × ULN. * Bilirubin ≤ 1.5 × ULN (except participants with documented Gilbert's syndrome who may be enrolled if the conjugated bilirubin is within normal limits) or ≤ 5 × ULN with liver metastases. Phase 2 Inclusion Criteria 13\. NSCLC : * Histologically or cytologically documented findings consistent with NSCLC not amenable to curative surgery, radiation, or other therapy. * Biomarker confirmed as PD-L1+ per local institutional standard practice. * Patients with known activating EGFR, STK11 or KEAP1 mutations as well as ALK/ROS1 fusions, are not eligible. * Prior treatment (for advanced, metastatic or \[neo\]adjuvant) should have included a platinum-based therapy and a PD-1/L1 pathway checkpoint inhibitor, unless the patient is not a candidate for or has refused viable therapies due to inability to tolerate treatment (i.e. cell therapy) or potential side effects (i.e. checkpoint inhibitor toxicity). 14\. Melanoma : Histologically or cytologically documented findings consistent with advanced cutaneous melanoma not amenable to curative surgery, radiation, or other therapy. Acral, mucosal and uveal melanoma are excluded. * Patients who are not candidates for or have refused available therapies due to inability to tolerate treatment (i.e. cell therapy) or potential side effects (i.e. checkpoint inhibitor toxicity) are also eligible. * Received an anti-PD-1/PD-L1 inhibitor as monotherapy or in combination with anti-CTLA-4 inhibitor and have either primary or secondary checkpoint inhibitor resistance asper SITC consensus definition, unless deemed intolerable by the Investigator. Patients with BRAF V600E mutant melanoma should have received a BRAF inhibitor as monotherapy or in combination with other targeted agents (MAPK kinase MEK inhibitors), unless deemed intolerable by the Investigator.
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of TEAEs, SAEs, and DLTs | From time of informed consent until 30 days after the last dose of investigational product. | — |
| Occurrence of changes from baseline in patients' clinical safety laboratory values and vital signs to assess the safety and tolerability of STX-003. | From Day 1 until 30 days after last dose of STX-003 | Collection and analysis of changes in data from baseline of patients' safety laboratory values (chemistry, hematology, coagulation, complement (Bb \& C3a), urinalysis, and lipids). Vital signs will include Temperature: (degrees Fahrenheit) Pulse: (beats per minute) Respiratory rate: (breaths per minute) Blood pressure: (systolic and diastolic each reported in mmHg) Oxygen saturation by pulse oximetry: (percentage (SpO2, %)) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of PK and PD in patients dosed with STX-003 | Day 1,2,3,4,8,15,22,23,24,25,29,36, 43,44,51,58 | Area under the concentration curve (AUC) |
| Number and nature of preliminary antitumor activity of STX-003 as monotherapy and in combination with Pembrolizumab. | From time of informed consent until 30 days after the last dose of investigational product. | — |
| Assessment of Tumor infiltrating lymphocytes | From time if informed consent until 30 days after the last dose of investigational product (STX-003) | Tumor biopsies will be analyzed by immunohistochemistry to assess tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment, including density of CD4 and CD8 positive cells and PD-L1 expression. |
| Objective Response Rate (ORR) in patients with advanced solid tumors. | From time of informed consent until 30 days after the last dose of investigational product. | — |
| Changes from baseline in vital signs | From Day 1 until 30 days after last dose of STX-003. | Vital signs will include Temperature: (degrees Fahrenheit) Pulse: (beats per minute) Respiratory rate: (breaths per minute) Blood pressure: (systolic and diastolic each reported in mmHg) Oxygen saturation by pulse oximetry: (percentage (SpO2, %)) |
Countries
United States
Contacts
CONTACTJason Luke, MD, Chief Medical Officer
Outcome results
None listed