Clinical trial NCT04440735: A Study of DSP107 Alone and in Combination with Atezolizumab for Patients with Advanced Solid Tumors
Official title: A First-in-Human, Two-Part, Open-Label, 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Non Small Cell Lung Cancer
Colorectal Cancer
Lead sponsor: Kahr Medical
Sponsor class: INDUSTRY
First posted: 2020-06-22
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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 purpose: TREATMENT

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.

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 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.

Eligibility criteria: 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

Primary outcomes:
measure: Adverse Events (AEs)
timeFrame: Duration of the study, estimated to be 9 months
measure: Dose Limiting Toxicities (DLT)
timeFrame: At the end of Treatment Cycle 1 (each cycle is 21 days)
measure: DSP107 Serum Concentration
timeFrame: At the end of Treatment Cycle 8 (each cycle is 21 days)
Secondary outcomes:
measure: DSP107 Effect on Phenotypic and Activation Profiles of Peripheral Blood Mononuclear Cells
timeFrame: At the end of Treatment Cycle 8 (each cycle is 21 days)
measure: DSP107 and atezolizumab anti-drug antibody (ADA) formation
timeFrame: Duration of the study, estimated to be 9 months
measure: Preliminary Efficacy (Part 2 only)
timeFrame: Duration of the study, estimated to be 12 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Moores Cancer Center, UCSD
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital, Anschutz Cancer Pavilion (ACP)
state: Colorado
city: Lake Mary
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center
state: Indiana
city: Kansas City
country: United States
facility: KUCC / KUMCRI University of Kansas Cancer Center
state: Kansas
city: Philadelphia
country: United States
facility: SKCC-Sidney Kimmel Cancer Center Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Jason Luke, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh
name: Anwaar Saeed, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: KUMC
name: Jun Zhang, MD
role: PRINCIPAL_INVESTIGATOR
References: