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

NCT04440735 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: DSP107_001
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 7

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 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.

Conditions

Advanced Solid Tumor; Non Small Cell Lung Cancer; Colorectal Cancer

Outcome Measures

Primary Outcomes (3)

• 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.

  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

  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

  At the end of Treatment Cycle 8 (each cycle is 21 days)

Secondary Outcomes (3)

• DSP107 Effect on Phenotypic and Activation Profiles of Peripheral Blood Mononuclear Cells

  At the end of Treatment Cycle 8 (each cycle is 21 days)

• DSP107 and atezolizumab anti-drug antibody (ADA) formation

  Duration of the study, estimated to be 9 months

• Preliminary Efficacy (Part 2 only)

  Duration of the study, estimated to be 12 months

Study Arms (5)

DSP107 monotherapy in advanced solid tumors

EXPERIMENTAL

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.

Biological: DSP107

DSP107 in combination with atezolizumab in advanced solid tumors

EXPERIMENTAL

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.

Biological: DSP107; Biological: Atezolizumab

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

EXPERIMENTAL

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.

Biological: DSP107; Biological: Atezolizumab

DSP107 monotherapy in colorectal cancer

EXPERIMENTAL

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..

Biological: DSP107

DSP107 in combination with atezolizumab in colorectal cancer

EXPERIMENTAL

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.

Biological: DSP107; Biological: Atezolizumab

Interventions

DSP107 BIOLOGICAL

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

DSP107 in combination with atezolizumab in advanced solid tumors; DSP107 in combination with atezolizumab in colorectal cancer; DSP107 in combination with atezolizumab in non-small cell lung cancer; DSP107 monotherapy in advanced solid tumors; DSP107 monotherapy in colorectal cancer

Atezolizumab BIOLOGICAL

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

DSP107 in combination with atezolizumab in advanced solid tumors; DSP107 in combination with atezolizumab in colorectal cancer; DSP107 in combination with atezolizumab in non-small cell lung cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Kahr Medical: lead

Study Sites (7)

Moores Cancer Center, UCSD

La Jolla, California, 92093, United States

Location

University of Colorado Hospital, Anschutz Cancer Pavilion (ACP)

Aurora, Colorado, 80045, United States

Location

Florida Cancer Specialists

Lake Mary, Florida, 32746, United States

Location

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

KUCC / KUMCRI University of Kansas Cancer Center

Kansas City, Kansas, 66204, United States

Location

SKCC-Sidney Kimmel Cancer Center Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

UPMC Hillman Cancer Center University of Pittsburgh

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Jason Luke, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

• Anwaar Saeed, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

• Jun Zhang, MD

  KUMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 16, 2020
• First Posted: June 22, 2020
• Study Start: October 7, 2020
• Primary Completion: September 1, 2025
• Study Completion: September 1, 2025
• Last Updated: January 9, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)