A Study of DSP107 Alone and in Combination with Atezolizumab for Patients with Advanced Solid Tumors

NCT ID: NCT04440735

Last Updated: 2025-01-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

125 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-10-07

Study Completion Date

2025-09-30

Brief Summary

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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 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.

Detailed Description

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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.

Conditions

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Advanced Solid Tumor Non Small Cell Lung Cancer Colorectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Part 1 will involve sequential enrollment 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 will comprise 2 expansion cohorts:

Expansion cohort A will involve enrollment of patients in a single arm receiving DSP107 in combination with atezolizumab.

Expansion cohort B will involve enrollment of patients randomized to receive either DSP107 monotherapy or DSP107 in combination with atezolizumab.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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DSP107 monotherapy in advanced solid tumors

DSP107 will be administered by intravenous infusion over 1 hour on Days 1, 8 and 15 of each 21-day cycle for up to 12 treatment cycles. Starting dose will be 0.01 mg/kg and maximum dose will not exceed 10 mg/kg.

Group Type EXPERIMENTAL

DSP107

Intervention Type BIOLOGICAL

DSP107 (SIRPα - 4-1BBL) is a bi-functional, trimeric, fusion protein.

DSP107 in combination with atezolizumab in advanced solid tumors

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. The study will include up to 12 treatment cycles.

Group Type EXPERIMENTAL

DSP107

Intervention Type BIOLOGICAL

DSP107 (SIRPα - 4-1BBL) is a bi-functional, trimeric, fusion protein.

Atezolizumab

Intervention Type BIOLOGICAL

Atezolizumab is a humanized IgG1 monoclonal antibody that targets PD-L1

DSP107 in combination with atezolizumab in non-small cell lung cancer

DSP107 10mg/kg 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. The study will include up to 12 treatment cycles.

Group Type EXPERIMENTAL

DSP107

Intervention Type BIOLOGICAL

DSP107 (SIRPα - 4-1BBL) is a bi-functional, trimeric, fusion protein.

Atezolizumab

Intervention Type BIOLOGICAL

Atezolizumab is a humanized IgG1 monoclonal antibody that targets PD-L1

DSP107 monotherapy in colorectal cancer

DSP107 10mg/kg will be administered by intravenous infusion over 1 hour on Days 1, 8 and 15 of each 21-day cycle for up to 12 treatment cycles..

Group Type EXPERIMENTAL

DSP107

Intervention Type BIOLOGICAL

DSP107 (SIRPα - 4-1BBL) is a bi-functional, trimeric, fusion protein.

DSP107 in combination with atezolizumab in colorectal cancer

DSP107 10mg/kg 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. The study will include up to 12 treatment cycles.

Group Type EXPERIMENTAL

DSP107

Intervention Type BIOLOGICAL

DSP107 (SIRPα - 4-1BBL) is a bi-functional, trimeric, fusion protein.

Atezolizumab

Intervention Type BIOLOGICAL

Atezolizumab is a humanized IgG1 monoclonal antibody that targets PD-L1

Interventions

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DSP107

DSP107 (SIRPα - 4-1BBL) is a bi-functional, trimeric, fusion protein.

Intervention Type BIOLOGICAL

Atezolizumab

Atezolizumab is a humanized IgG1 monoclonal antibody that targets PD-L1

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Subject must have measurable disease per RECIST version 1.1
* 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
* Part 2, Expansion Cohort A:

* 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 (e.g., ALK, EGFR, ROS1, RET, NTRK). Driver mutations for KRAS, BRAF and c-METex14skip will be allowed.
* Received no more than 2 lines of prior systemic treatment, including anti PD-1 or anti PD-L1 therapeutic agent ± chemotherapy. Targeted therapies for KRAS, BRAF and c-METex14skip will not be counted towards the previous lines of therapy.
* Part 2, Expansion Cohort B:

* Histologically confirmed, inoperable microsatellite stable colorectal carcinoma (Stage 3b or Stage 4)
* Received two previous lines of therapy including standard chemotherapy and/or targeted antibodies

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Kahr Medical

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jason Luke, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Anwaar Saeed, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Jun Zhang, MD

Role: PRINCIPAL_INVESTIGATOR

KUMC

Locations

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Moores Cancer Center, UCSD

La Jolla, California, United States

Site Status

University of Colorado Hospital, Anschutz Cancer Pavilion (ACP)

Aurora, Colorado, United States

Site Status

Florida Cancer Specialists

Lake Mary, Florida, United States

Site Status

Indiana University Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

KUCC / KUMCRI University of Kansas Cancer Center

Kansas City, Kansas, United States

Site Status

SKCC-Sidney Kimmel Cancer Center Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

UPMC Hillman Cancer Center University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Countries

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United States

Other Identifiers

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DSP107_001

Identifier Type: -

Identifier Source: org_study_id

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