Anal Cancer Metastatic, Squamous Cell Carcinoma of the Anus Stage Unspecified, Pancreatic Cancer Metastatic, Unresectable Pancreatic Carcinoma
Conditions
Brief summary
This is an open-label, phase 1/2, multiple-indication platform study to explore safety, potential predictive immune-related biomarkers, and early efficacy (as measured by objective response rate \[ORR; Cohorts 1,2, 4,and 5\] and disease control rate \[DCR; Cohort 3\]) in patients with advanced or metastatic gastrointestinal (GI) tumors. Cohorts 1-4 are not randomized; however, Cohort 5 is comprised of two treatment arms to which patients are randomized in a 1:1 ratio.
Detailed description
The overall aim is to assess safety, predictive biomarkers, and preliminary efficacy as assessed by tumor response criteria at week 16 for cohorts1, 2, 3, and 4, and best overall response rate and OS in Cohort 5. If a cohort shows a promising ORR in Stage 1 of the Simon two-stage design, that cohort may be expanded to enroll additional patients (up to 50 patients in Cohorts 1 and 3 , up to 28 patients in Cohort 4, and up to 64 patients in Cohort 5) in an extension phase per predetermined statistical conditions. In addition, either or both arms of Cohort 5 may expand if the data collected in Stage 1 suggest that expansion may help in assessing the potential survival benefit of the investigational therapy(ies). In this study, we hypothesize that treatment with pelareorep will prime the tumor microenvironment (TME) for checkpoint blockade therapy, thereby increasing PD-L1 expression and the number of new T cell clones within the tumor, both of which are associated with increased response to checkpoint blockade.
Interventions
DRUGPelareorep
Pelareorep 4.5 x 10\^10 TCID50 via 1-hour IV infusion
DRUGAtezolizumab
Atezolizumab 840 mg IV infusion
Gemcitabine (1,000 mg/m2) and nab-paclitaxel (125 mg/m2)
Trifluridine/tipiracil administered at a 35 mg/m2 dose orally twice daily
mFOLFIRINOX- IV oxaliplatin 85 mg/m2; IV leucovorin 400 mg/m2; IV irinotecan 150 mg/m2; 5-FU 2400 mg/m2 by 46-hour infusion, per local standard of care
Sponsors
Crolll Gmbh
AIO-Studien-gGmbH
Oncolytics Biotech
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
Cohorts 1-5 Inclusion Criteria: * ECOG performance status of 0 or 1 * Have measurable lesions per RECIST v1.1 * Patients must have adequate hematological, renal, and hepatic function * Have recovered to ≤grade 1 or baseline for all adverse events (AEs) due to previous therapies or surgeries. * For female patients of childbearing potential and male patients with partners of childbearing potential, agreement to use a highly-effective form(s) of contraception and to continue its use for 6 months after the last dose of study drug.
Exclusion criteria
* Undergone systemic chemotherapy, radiotherapy, or surgery, \<4 weeks before study treatment. * Received previous treatment with immune checkpoint inhibitors * Uncontrolled or severe cardiac disease * Active, uncontrolled infections * Symptomatic brain metastasis * Interstitial lung disease with symptoms or signs of activity. * Autoimmune disease that has required systemic treatment in the past 2 years with disease modifying agents, corticosteroids, or immunosuppressive drugs. * A seizure disorder that requires pharmacotherapy. * Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation. * A non-healing wound, non-healing ulcer, or non-healing bone fracture within 4 weeks prior to the start of study drug. * Women who are pregnant or breastfeeding. * A diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy * Any vaccine within 28 days prior to first treatment or during the first cycle of study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) for Cohort 1, 2, 4, and 5 | At week 16 (within each cohort) | Proportion of patients with complete response \[CR\], partial response \[PR\] assessed by the investigators and/or central reader according to RECIST v1.1 |
| Disease Control Rate (DCR) - Cohort 3 | at week 16 | DCR (complete response \[CR\], partial response \[PR\], and stable disease \[SD\]) assessed by the investigators according to RECIST v 1.1. |
| Overall Survival (OS) - Cohort 5 | Cohort 5: From the date of randomization through long term follow up at 2 years | OS is defined as the time from date of first treatment to death from any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) - Cohort 1-4 | From initiation of treatment to disease progression or death from any cause, whichever occurs first, up to two years | ORR, defined as the percentage of patients with a best overall response of complete response \[CR\] or partial response \[PR\] according to RECIST v 1.1, and confirmed ORR, defined as the percentage of patients with a CR or PR at two or more consecutive evaluation timepoints. |
| Progression Free Survival (PFS) | From initiation of treatment to objective progression or death from any cause, whichever occurs first, up to two years | Time from the first dose date of study treatment to the date of investigator-determined objective progression (according to RECIST 1.1) or death from any cause, whichever occurs first. |
| Overall Survival (OS) - Cohort 1-4 | From the date of randomization through long term follow up at 3 years | OS defined as the time from date of first treatment to death from any cause |
| Duration of Response (DOR) | From initiation of treatment to disease progression or death from any cause, whichever occurs first, up to two years | Time from documentation of the first CR or PR to the time of first documented evidence of progressive disease (or relapse for subjects who experience CR during the study) or death. |
| Disease Control Rate (DCR) | From initiation of treatment to disease progression or death from any cause, whichever occurs first, up to two years | Overall DCR, defined as the number of patients with a best overall response of CR, PR, or SD according to RECIST v. 1.1. |
Countries
Germany
Contacts
Primary ContactReference Study ID Number: REO 029 GOBLET
Outcome results
None listed