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

Phase 1

Active, not recruiting

• Conditions: Advanced Solid Tumor; Colorectal Cancer; Non Small Cell Lung Cancer
• Interventions: Biological: DSP107; Biological: Atezolizumab

• Registration Number: NCT04440735
• Lead Sponsor: Kahr Medical

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.

Study Timeline

• Study First Submitted: 2020-06-16
• Study First Submitted QC: 2020-06-17
• Study First Posted: 2020-06-22
• Study Start: 2020-10-07
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-07
• Last Update Posted: 2025-01-09
• Primary Completion: 2025-09
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 125

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
DSP107 in combination with atezolizumab in advanced solid tumors	DSP107	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.
DSP107 in combination with atezolizumab in advanced solid tumors	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. The study will include up to 12 treatment cycles.
DSP107 monotherapy in advanced solid tumors	DSP107	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.
DSP107 in combination with atezolizumab in non-small cell lung cancer	DSP107	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.
DSP107 monotherapy in colorectal cancer	DSP107	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..
DSP107 in combination with atezolizumab in non-small cell lung cancer	Atezolizumab	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.
DSP107 in combination with atezolizumab in colorectal cancer	DSP107	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.
DSP107 in combination with atezolizumab in colorectal cancer	Atezolizumab	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.

Primary Outcome Measures

Name	Time	Method
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.
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
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

Name	Time	Method
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.
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.
Preliminary Efficacy (Part 2 only)	Duration of the study, estimated to be 12 months	Patients will undergo computed tomography (CT) scans to allow assessment of tumor response according to RECIST criteria

Trial Locations

Locations (7)

Moores Cancer Center, UCSD; 🇺🇸 La Jolla, California, United States

University of Colorado Hospital, Anschutz Cancer Pavilion (ACP); 🇺🇸 Aurora, Colorado, United States

Florida Cancer Specialists; 🇺🇸 Lake Mary, Florida, United States

Indiana University Simon Cancer Center; 🇺🇸 Indianapolis, Indiana, United States

KUCC / KUMCRI University of Kansas Cancer Center; 🇺🇸 Kansas City, Kansas, United States

SKCC-Sidney Kimmel Cancer Center Thomas Jefferson University; 🇺🇸 Philadelphia, Pennsylvania, United States

UPMC Hillman Cancer Center University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States