A Study of DSP107 Alone and in Combination With Atezolizumab for Patients With Advanced Solid Tumors
Study Details
Study Description
Brief Summary
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 single agent treatment and DSP107 in combination with atezolizumab in second line treatment of non small cell lung cancer
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
Detailed Description
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 a single expansion cohort consisting of two treatment arms in which subjects will be treated either with DSP107 monotherapy or DSP107 in combination with atezolizumab. This part of the study will enrol subjects with non small cell lung cancer who have progressed following first line treatment with PD-1 or PD-L1 targeting agents having previously achieved a best response of stable disease or better.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: DSP107 monotherapy DSP107 will be administered by intravenous infusion over 1 hour on Days 1, 8 and 15 of each 21-day cycle. The study will include up to 12 treatment cycles. Starting dose will be 0.01 mg/kg and maximum dose will not exceed 10 mg/kg. |
Biological: DSP107
DSP107 (SIRPα - 4-1BBL) is a bi-functional, trimeric, fusion protein.
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Experimental: DSP107 in combination with atezolizumab DSP107 will be administered by IV infusion over 1 hour on Days 1, 8 and 15 of each 21-day cycle. Subjects will receive atezolizumab 1200 mg by intravenous infusion over 30 mins (first infusion over 1 hour) on Day 1 of every treatment cycle. DSP107 infusion will commence 1 hour following completion of atezolizumab infusion. |
Biological: DSP107
DSP107 (SIRPα - 4-1BBL) is a bi-functional, trimeric, fusion protein.
Biological: Atezolizumab
Atezolizumab is a humanized IgG1 monoclonal antibody that targets PD-L1
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Outcome Measures
Primary Outcome Measures
- Adverse Events (AEs) [Duration of the study, estimated to be 9 months]
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.
- Dose Limiting Toxicities (DLT) [At the end of Treatment Cycle 1 (each cycle is 21 days)]
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
- DSP107 Serum Concentration [At the end of Treatment Cycle 8 (each cycle is 21 days)]
Serum samples will be collected to determine circulating levels and PK profile of DSP107
Secondary Outcome Measures
- DSP107 Effect on Phenotypic and Activation Profiles of Peripheral Blood Mononuclear Cells [At the end of Treatment Cycle 8 (each cycle is 21 days)]
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.
- DSP107 and atezolizumab anti-drug antibody (ADA) formation [Duration of the study, estimated to be 9 months]
Serum samples will be collected throughout the study for assessment of ADA formation using validated assay.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
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Subject must have measurable disease per RECIST version 1.1
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Part 1:
o Histologically confirmed advanced solid tumor that is not amenable to surgical resection or other approved therapeutic options that have demonstrated clinical benefit or subject is intolerant or has refused available therapies
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Part 2:
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Histologically confirmed, inoperable non-small cell lung cancer (Stage 3b or Stage 4)
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Squamous and non-squamous histologies are both acceptable
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Wildtype for actionable oncogenic driver mutations
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Received first line treatment including anti PD-1 or anti PD-L1 therapeutic agent ± chemotherapy and achieved a best response of stable disease measured after 12 weeks of treatment
Exclusion Criteria:
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Life expectancy of ≤ 3 months
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Central nervous system (CNS) metastases
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Life-threatening (grade 4) immune-mediated adverse event related to prior immunotherapy
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Immune-mediated adverse reaction that required discontinuation of prior immunotherapy
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Past or current history of autoimmune disease or immune deficiency
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History of autoimmune hemolytic anemia or autoimmune thrombocytopenia
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History of hematological malignancy
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History of organ or stem cell transplantation
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Clinically significant liver disease, including alcoholic hepatitis, cirrhosis, fatty liver disease and inherited liver disease
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Previously treatment with CAR-T cells
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Treatment with systemic immunosuppressive medication within 2 weeks prior to first dose of study treatment
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Received live, attenuated vaccine within 4 weeks prior to first dose of study treatment
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Treatment with systemic immunostimulatory agents within 4 weeks prior to first dose of study treatment
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Treatment with atezolizumab, any CD47/SIRPα targeting agent or immune agonists (e.g., anti-CD137, anti-CD40, anti-OX40)
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Known allergy or hypersensitivity to any of the test compounds, materials or contraindication to test product
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Clinically significant abnormal laboratory safety tests
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Detection of anti DSP107 antibodies at screening
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History of HIV infection or active Hepatitis B or C infection
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Pregnant or breast feeding or planning to become pregnant while enrolled in the study
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History or evidence of any other clinically unstable/uncontrolled disorder, condition, or disease
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Moores Cancer Center, UCSD | La Jolla | California | United States | 92093 |
2 | University of Colorado Hospital, Anschutz Cancer Pavilion (ACP) | Aurora | Colorado | United States | 80045 |
3 | KUCC / KUMCRI University of Kansas Cancer Center | Kansas City | Kansas | United States | 66204 |
4 | SKCC-Sidney Kimmel Cancer Center Thomas Jefferson University | Philadelphia | Pennsylvania | United States | 19107 |
5 | UPMC Hillman Cancer Center University of Pittsburgh | Pittsburgh | Pennsylvania | United States | 15232 |
Sponsors and Collaborators
- Kahr Medical
Investigators
- Principal Investigator: Jason Luke, MD, University of Pittsburgh
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- DSP107_001