A Study of DSP107 Alone and in Combination With Atezolizumab for Patients With Advanced Solid Tumors
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| ClinicalTrials.gov Identifier: NCT04440735 |
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Recruitment Status :
Recruiting
First Posted : June 22, 2020
Last Update Posted : March 31, 2022
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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 |
|---|---|---|
| Advanced Solid Tumor Non Small Cell Lung Cancer | Biological: DSP107 Biological: Atezolizumab | Phase 1 Phase 2 |
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 Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 100 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Intervention Model Description: | Part 1 will involve sequential enrolment of patient cohorts to investigate the safety of up to 7 potential dose levels. Dose escalation will commence with up to 3 single subject cohorts before moving to a 3 + 3 dose escalation scheme to determine the maximum tolerated dose and/or recommended phase II dose. Up to 3 additional dose finding cohorts will be enrolled in parallel to the monotherapy dose escalation to establish a safe dose of DSP107 when given in combination with atezolizumab. These dose-finding combination arms will start at least one dose level below a DSP107 monotherapy dose that has already been deemed safe. Part 2 information will be updated on completion of Part 1. |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase I/II Study of DSP107 in Subjects With Advanced Solid Tumors Including a Dose-escalation Safety Study (Part 1) and Preliminary Efficacy Assessment of DSP107 as Monotherapy and in Combination With Atezolizumab (Part 2) |
| Actual Study Start Date : | October 7, 2020 |
| Estimated Primary Completion Date : | June 2023 |
| Estimated Study Completion Date : | August 2023 |
| 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.
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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.
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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 |
- Adverse Events (AEs) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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
- DSP107 Effect on Phenotypic and Activation Profiles of Peripheral Blood Mononuclear Cells [ Time Frame: 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 [ Time Frame: 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- 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:
- Histologically confirmed, inoperable non-small cell lung cancer (Stage 3b or Stage 4)
- Squamous and non-squamous histologies are both acceptable
- Wildtype for actionable oncogenic driver mutations
- 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:
- Life expectancy of ≤ 3 months
- Central nervous system (CNS) metastases
- Life-threatening (grade 4) immune-mediated adverse event related to prior immunotherapy
- Immune-mediated adverse reaction that required discontinuation of prior immunotherapy
- Past or current history of autoimmune disease or immune deficiency
- History of autoimmune hemolytic anemia or autoimmune thrombocytopenia
- History of hematological malignancy
- History of organ or stem cell transplantation
- Clinically significant liver disease, including alcoholic hepatitis, cirrhosis, fatty liver disease and inherited liver disease
- Previously treatment with CAR-T cells
- Treatment with systemic immunosuppressive medication within 2 weeks prior to first dose of study treatment
- Received live, attenuated vaccine within 4 weeks prior to first dose of study treatment
- Treatment with systemic immunostimulatory agents within 4 weeks prior to first dose of study treatment
- Treatment with atezolizumab, any CD47/SIRPα targeting agent or immune agonists (e.g., anti-CD137, anti-CD40, anti-OX40)
- Known allergy or hypersensitivity to any of the test compounds, materials or contraindication to test product
- Clinically significant abnormal laboratory safety tests
- Detection of anti DSP107 antibodies at screening
- History of HIV infection or active Hepatitis B or C infection
- Pregnant or breast feeding or planning to become pregnant while enrolled in the study
- History or evidence of any other clinically unstable/uncontrolled disorder, condition, or disease
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04440735
| Contact: Yaffa Shwartz | +972506396356 | yaffa@kahr-medical.com | |
| Contact: Adam Foley-Comer, MD | +972547491753 | adam@kahr-medical.com |
| United States, California | |
| Moores Cancer Center, UCSD | Not yet recruiting |
| La Jolla, California, United States, 92093 | |
| Contact: Ashley Weaver 858-822-1962 aweaver@health.ucsd.edu | |
| Principal Investigator: Sandip Patel, MD | |
| United States, Colorado | |
| University of Colorado Hospital, Anschutz Cancer Pavilion (ACP) | Recruiting |
| Aurora, Colorado, United States, 80045 | |
| Contact: Aaron Parsons, BS, MS 720-848-4603 aaron.parsons@cuanschutz.edu | |
| Principal Investigator: Antonio Jimeno, MD | |
| United States, Kansas | |
| KUCC / KUMCRI University of Kansas Cancer Center | Recruiting |
| Kansas City, Kansas, United States, 66204 | |
| Contact: Lanecia Wright 913-588-4769 lwright9@kumc.edu | |
| Contact: Tina Liu tliu@kumc.edu | |
| Principal Investigator: Anwaar Saeed, MD | |
| United States, Pennsylvania | |
| SKCC-Sidney Kimmel Cancer Center Thomas Jefferson University | Recruiting |
| Philadelphia, Pennsylvania, United States, 19107 | |
| Contact: Tina Savio 215-955-6407 Tina.Savio@Jefferson.edu | |
| Contact: Aliya Rogers Aliya.Rogers@jefferson.edu | |
| Principal Investigator: Babar Bashir, MD | |
| UPMC Hillman Cancer Center University of Pittsburgh | Recruiting |
| Pittsburgh, Pennsylvania, United States, 15232 | |
| Contact: Sarah Brodeur 412-623-2944 brodeurs@upmc.edu | |
| Contact: Mallory Reed reedm7@upmc.edu | |
| Principal Investigator: Luke Jason, MD | |
| Principal Investigator: | Jason Luke, MD | University of Pittsburgh |
| Responsible Party: | Kahr Medical |
| ClinicalTrials.gov Identifier: | NCT04440735 |
| Other Study ID Numbers: |
DSP107_001 |
| First Posted: | June 22, 2020 Key Record Dates |
| Last Update Posted: | March 31, 2022 |
| Last Verified: | March 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Carcinoma, Non-Small-Cell Lung Neoplasms Carcinoma, Bronchogenic Bronchial Neoplasms Lung Neoplasms Respiratory Tract Neoplasms |
Thoracic Neoplasms Neoplasms by Site Lung Diseases Respiratory Tract Diseases Atezolizumab Antineoplastic Agents |