This is a phase I/IIA, first-in-human (FIH), two-part, open-label, multicenter study to characterize the safety, tolerability profile, and clinical efficacy of STC-1010 associated with GM-CSF and cyclophosphamide immunostimulant (IS) regimen administered with standard of care (SOC) therapy (mFOLFOX6 with or without bevacizumab) to participants with unresectable locally advanced (stage IIIC, T4b) or unresectable metastatic (stage IV) colorectal cancer (CRC).
The trial will be conducted in two parts:
* A Phase I consisting of a dose escalation part and small expansion part to determine the maximum tolerated dose (MTD), recommended Phase II dose (RP2D) and safety profile of the STC-1010 + IS regimen administered with SOC therapy. Approximately 21 to 33 participants will be included in this phase in Europe. * A Phase IIA consisting of the expansion stage of the study which will further evaluate the clinical efficacy and safety of STC-1010 on a larger number of participants treated at the identified RP2D. Approximately 57 to 60 participants will be enrolled in total in 2 different arms. Multi-site recruitment will take place in Europe and in the US.
Male or female aged 18-75 years
Histologically confirmed diagnosis of unresectable locally advanced (stage IIIC, T4b) or unresectable metastatic (stage IV) (R0) adenocarcinoma of the colon or rectum
Adjuvant fluoropyrimidine monotherapy or oxaliplatin-based chemotherapy allowed if more than 6 months have elapsed between the end of adjuvant treatment and first relapse
Determination of KRAS and BRAF mutation status
Patients with symptomatic ascites or pleural effusion
Dihydropyrimidine dehydrogenase (DPD) deficiency
Resectable tumor with curative intent or patient considered for a curative strategy by intensifying chemotherapy to induce resectability
Prior chemotherapy for metastatic disease
Sequential
STC-1010 + IS regimen + SOC therapy
Biological/VaccineSTC-1010 administered with immunostimulants (IS) in low-dose (cyclophosphamide and GM-CSF) and standard of care (SOC) therapy (mFOLFOX6 with or without bevacizumab)
Phase 1: To determine overall safety profile, recommended Phase 2 dose (RP2D) and maximum tolerated dose (MTD)
Endpoint/Outcome Measures: Incidence, severity, and relationship of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Dose-Limiting Toxicities (DLT) (in dose escalation part), AEs leading to treatment discontinuation; and clinically significant findings on clinical laboratory tests, vital signs, electrocardiograms (ECGs), and physical examinations, using the Common Terminology Criteria for Adverse Events (CTCAE Version 5).
Phase 2A: To determine the clinical efficacy by Progression Free Survival (PFS) rate
Progression Free Survival (PFS) rate at 12 months from STC-1010 + IS regimen initiation, defined as the proportion of participants alive and without progression (i.e., participants with complete response \[CR\], partial response \[PR\] or stable disease \[SD\]) at 12 months according to RECIST 1.1
Phase 1: To determine the preliminary clinical efficacy
Endpoints/Outcome Measures: Overall Response Rate (ORR) at 6 months from STC-1010 + IS treatment initiation, defined as the achievement of either a complete response (CR) or partial response (PR) according to RECIST 1.1; Progression Free Survival (PFS) rate at 6 months from STC-1010 + IS treatment initiation (defined as the rate of participants alive with CR, PR or SD) according to RECIST 1.1; and Median of PFS.
Phase 1: To describe the effects on cell-mediated immunity
Assessment of delayed-type hypersensitivity (DTH) score after the first vaccination (at 1, 24, 48 and 72 hours post-STC-1010 injection) and then after the 4th, 8th and every boost
Phase 2A: To determine the overall safety and tolerability profile
Endpoints/Outcome Measures: Incidence, severity and relationship of TEAEs, SAEs, TEAEs leading to discontinuation of study treatment; and clinically significant findings on clinical laboratory tests, vital signs, ECGs and physical examinations, using the CTCAE Version 5.
Phase 2A: To determine the clinical efficacy by Clinical Benefit Rate (CBR)
Clinical Benefit Rate (CBR) defined as the percentage of participants in whom the best response is CR or PR, or SD lasting for a least 6 months.
Phase 1: To determine the impact on immune and molecular biomarkers (exploratory outcomes)
Assessment of biomarkers in blood and tumor biopsies
Phase 2: To determine the impact on immune and molecular biomarkers (exploratory outcomes)
Assessment of biomarkers in blood and tumor biopsies
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