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

Sponsor
Kahr Medical (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04440735
Collaborator
(none)
100
5
2
33.8
20
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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
  • Biological: DSP107
  • Biological: Atezolizumab
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

Study Type:
Interventional
Anticipated 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.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 :
Oct 7, 2020
Anticipated Primary Completion Date :
Jun 1, 2023
Anticipated Study Completion Date :
Aug 1, 2023

Arms and Interventions

Arm Intervention/Treatment
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.

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

Outcome Measures

Primary Outcome Measures

  1. 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.

  2. 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

  3. 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

  1. 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.

  2. 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

Ages Eligible for Study:
18 Years and Older
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

  • 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:

  • 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

Contacts and Locations

Locations

Site City State Country Postal Code
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.
Responsible Party:
Kahr Medical
ClinicalTrials.gov Identifier:
NCT04440735
Other Study ID Numbers:
  • DSP107_001
First Posted:
Jun 22, 2020
Last Update Posted:
Mar 31, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Mar 31, 2022