Colorectal Cancer
Conditions
Brief summary
This clinical study is testing whether a new combination of medicines (DSP107 and atezolizumab) is more effective and safer than an existing treatment (fruquintinib) for people with advanced colorectal cancer that is microsatellite stable (MSS). Participants will be randomly assigned to receive one of the two treatments, and researchers will monitor how well the cancer responds, how safe the treatments are, and how the body processes them. The study hopes to show that the new combination can improve outcomes for patients with this type of colorectal cancer.
Detailed description
This Phase 2b, randomized, open-label, multicenter study will enroll participants with advanced MSS or mismatch repair-proficient (pMMR) colorectal cancer who have progressed on, or shown intolerance to, standard therapies, including fluoropyrimidine, irinotecan, oxaliplatin, trifluridine/tipiracil (Lonsurf), bevacizumab, and epidermal growth factor receptor (EGFR) inhibitors if RAS wild-type. Participants with BRAF V600E mutation, HER2 amplification/overexpression, KRAS G12C mutation, RET fusion, or NTRK fusion may also have received one prior targeted therapy. Prior treatment with fruquintinib or regorafenib is not allowed. Participants will be randomized 1:1 into two arms: Group A (Experimental): DSP107 10 mg/kg intravenously on Days 1, 8, and 15 of each 28-day cycle, administered after atezolizumab 1680 mg IV on Day 1 of each cycle. DSP107 infusion may be shortened after initial tolerance. Atezolizumab infusion may be shortened from 60 to 30 minutes if well tolerated. Group B (Active Comparator): Fruquintinib 5 mg orally once daily on Days 1-21 of each 28-day cycle, with dosing diaries maintained by participants. Total duration of study participation for each participant will vary based on factors including treatment tolerability, disease progression and other study discontinuation criteria. Study duration for participants will include at least: * Screening Period of up to 28 days * Treatment Period of up to 24 cycles of 28 days * Safety Follow-up Period of up to 90 days\* from the last dose of IP or active comparator. * LTFU for a period of up to 5 years from randomization.
Interventions
DRUGDSP107 + Atezolizumab
DSP107 infusion begins \~30 (±10) minutes after completion of atezolizumab infusion on Day 1.
DRUGFruquintinib
5 mg orally, once daily (with or without food), on Days 1-21 of each 28-day cycle, followed by 7 days off.
Sponsors
Kahr Bio Australia Pty Ltd
Novotech (Australia) Pty Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Are ≥ 18 years of age with a life expectancy of \> 3 months. 2. Participants with histologically confirmed, inoperable, MSS and/or pMMR CRC which has progressed to, or is intolerant to, specified therapies (and has received prior treatment with no more than 3 lines of therapy). 3. Measurable disease per RECIST v1.1.
Exclusion criteria
1. Central nervous system (CNS) metastases unless stable 2 months post definitive therapy with steroids. 2. Unresolved AEs of Grade 2 or higher from prior anticancer therapy. 3. Past or current history of autoimmune disease or immune deficiency. 4. History of other malignancy within 3 years of first study treatment cycle. 5. Current or recent treatment with certain therapies including specified anticancer treatments, modulators of CYP3A4 and immunomodulating therapies (prior treatment with CPIs is not exclusory). 6. Known allergy or hypersensitivity to any of the test compounds, materials, or contraindication to test product. 7. Clinically significant abnormal laboratory safety tests.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To determine Median overall survival (mOS) in participants treated with the combination of DSP107 and atezolizumab versus fruquintinib. | From Day 1 until date of death from any cause assessed up to 2 years | Median Overall Survival (mOS) will be estimated using Kaplan-Meier methodology as the median time from the start of study treatment to the last known date a participant was alive. Censoring rules will be applied for participants without an event at the time of analysis, and 95% confidence intervals for mOS will be provided. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of adverse events (AEs) | From Screening to Follow-up (30 to 90 Days Post IP) | Safety and tolerability of DSP107 + atezolizumab versus fruquintinib, assessed by incidence and severity of AEs per CTCAE v5.0 (including SAEs and AESIs). |
| Changes in 12-lead ECG parameters | From Baseline through to end of treatment visit, an average of 6 months | Safety assessment based on changes from baseline in ECG intervals (PR, QRS, QT, QTc) and heart rate. |
| Change in Overall Survival (OS) | From randomization through study participation, with survival follow up at approximately 4-month (± 1 month) intervals for up to 5 years from randomization | All randomized participants will continue to the LTFU phase of the study to allow determination of overall survival |
| Change from Baseline in Quality of Life (QoL) | From Baseline through to end of treatment visit, an average of 6 months | Evaluation of the effect of treatment on quality of life (QoL) using the Functional Assessment of Cancer Therapy - Colorectal (FACT-C). |
| Change from Baseline in Systolic and Diastolic Blood Pressure | From Baseline through to end of treatment visit, an average of 6 months | Mean change from baseline in blood pressure (mmHg). |
| Change from Baseline in Pulse Rate | From Baseline through to end of treatment visit, an average of 6 months | Mean change from baseline in heart rate (beats per minute). |
| To evaluate the immunogenicity of DSP107 when administered in combination with atezolizumab. | From Baseline through to end of treatment visit, an average of 6 months | Immunogenicity will be assessed by measurement of anti-drug antibodies (ADAs) to DSP107 in serum samples collected at specified time points. |
Countries
Australia, United States
Contacts
CONTACTAdam Foley Comer
Outcome results
None listed