Part 1: A first-in-human, open-label, Phase I dose escalation study of DSP107 monotherapy and combination therapy with atezolizumab in patients with advanced solid tumors. Part 2: Preliminary efficacy assessment of DSP107 in combination with atezolizumab in second or third line treatment of non small cell lung cancer. Preliminary efficacy assessment of DSP107 as a single agent or in combination with atezolizumab in third line treatment of colorectal cancer.
This study will be the first time that DSP107 is administered to human subjects. The aim of the study is to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of DSP107 monotherapy and combination therapy in a two-part design. Part 1 will involve DSP107 monotherapy dose escalation in subjects with advanced solid tumors that are not amenable to surgical resection or other approved therapeutic options that have demonstrated clinical benefit. Additional dose finding cohorts will be enrolled to establish a safe dose of DSP107 when given in combination with atezolizumab. Part 2 will comprise two expansion cohorts: A) Expansion cohort A consisting of one treatment arm in which subjects will be treated with DSP107 in combination with atezolizumab. This expansion cohort will enroll subjects with non small cell lung cancer who have progressed following no more than 2 lines of prior systemic treatment including treatment with PD-1 or PD-L1 targeting agents. B) Expansion cohort B consisting of two treatment arms in which subjects will be treated either with DSP107 monotherapy or DSP107 in combination with atezolizumab. This expansion cohort will enroll subjects with colorectal cancer who have progressed following two previous lines of therapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
125
DSP107 (SIRPα - 4-1BBL) is a bi-functional, trimeric, fusion protein.
Atezolizumab is a humanized IgG1 monoclonal antibody that targets PD-L1
Moores Cancer Center, UCSD
La Jolla, California, United States
University of Colorado Hospital, Anschutz Cancer Pavilion (ACP)
Aurora, Colorado, United States
Florida Cancer Specialists
Lake Mary, Florida, United States
Indiana University Simon Cancer Center
Indianapolis, Indiana, United States
KUCC / KUMCRI University of Kansas Cancer Center
Kansas City, Kansas, United States
SKCC-Sidney Kimmel Cancer Center Thomas Jefferson University
Philadelphia, Pennsylvania, United States
UPMC Hillman Cancer Center University of Pittsburgh
Pittsburgh, Pennsylvania, United States
Adverse Events (AEs)
An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time frame: Duration of the study, estimated to be 9 months
Dose Limiting Toxicities (DLT)
A DLT is defined as a clinically significant AE of laboratory abnormality that is related to DSP107 or the combination of DSP107 and atezolizumab, but is unrelated to disease progression, intercurrent illness or concomitant medications
Time frame: At the end of Treatment Cycle 1 (each cycle is 21 days)
DSP107 Serum Concentration
Serum samples will be collected to determine circulating levels and PK profile of DSP107
Time frame: At the end of Treatment Cycle 8 (each cycle is 21 days)
DSP107 Effect on Phenotypic and Activation Profiles of Peripheral Blood Mononuclear Cells
Blood samples will be collected and examined by flow cytometry to determine the effect of DSP107 on different T-cells, B-cells, NK cells and monocytes, and their expression of activation markers.
Time frame: At the end of Treatment Cycle 8 (each cycle is 21 days)
DSP107 and atezolizumab anti-drug antibody (ADA) formation
Serum samples will be collected throughout the study for assessment of ADA formation using validated assay.
Time frame: Duration of the study, estimated to be 9 months
Preliminary Efficacy (Part 2 only)
Patients will undergo computed tomography (CT) scans to allow assessment of tumor response according to RECIST criteria
Time frame: Duration of the study, estimated to be 12 months
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