Colon Cancer, Metastatic Colorectal Cancer, Rectal Cancer
Conditions
Keywords
DEM301, antibody-drug conjugate (ADC), ADC, metastatic colorectal cancer (mCRC), mCRC, colon cancer, rectal cancer
Brief summary
This is a first-in-human Phase 1 study of DEM301 in adults with previously treated advanced metastatic colorectal cancer. DEM301 is an investigational antibody-drug conjugate. The study will evaluate the safety and tolerability of DEM301, identify doses for further study, and assess how the drug behaves in the body and whether it shows signs of activity against the cancer.
Detailed description
This is a Phase 1, multicenter, open-label study of DEM301 in participants with previously treated advanced metastatic colorectal cancer. The study has two parts: Dose Escalation, and Dose Expansion. Dose Escalation will evaluate the safety and tolerability of DEM301 and identify one or more recommended doses for further study. Dose Expansion will further evaluate DEM301 at the selected dose or doses. The study will also assess preliminary antitumor activity, pharmacokinetics, immunogenicity, pharmacodynamic effects, and exploratory biomarkers. Approximately 60 participants are planned.
Interventions
DRUGDEM301
DEM301 is an investigational antibody-drug conjugate being evaluated as monotherapy in Dose Escalation and Dose Expansion cohorts.
Sponsors
DEM BioPharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study consists of sequential Dose Escalation and Dose Expansion components. DEM301 will initially be evaluated in dose escalation cohorts. Based on available study data, one or more recommended doses will be selected for further evaluation in Dose Expansion.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years. 2. Participants must have documented advanced (metastatic or unresectable) colorectal cancer that has progressed on or after prior standard-of-care treatment and must have received, or been unable to receive, applicable standard therapies as defined in the protocol. 3. Life expectancy ≥12 weeks. 4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 5. Have at least 1 measurable lesion at baseline suitable for repeat imaging evaluation by RECIST v1.1. 6. Adequate bone marrow, liver, kidney, and coagulation function per protocol requirements. 7. Agree to provide adequate tumor tissue for protocol-required biomarker assessment. Participants in designated cohorts must be willing to provide fresh tumor biopsies, unless medically contraindicated. 8. Female participants must not be pregnant or breastfeeding. Male and female participants must comply with protocol-defined reproductive and contraception requirements. 9. Have suitable venous access for study treatment and required blood sampling. 10. Be willing and able to comply with study assessments, schedule, and restrictions. 11. Written informed consent must be obtained before any study-related procedures are performed.
Exclusion criteria
1. Prior treatment with certain antibody-drug conjugates, as defined in the protocol. Protocol-defined exceptions may apply. 2. Recent anticancer therapy, investigational treatment, major surgery, or radiation therapy within the protocol-defined washout periods. 3. Ongoing clinically significant toxicity from prior therapy that has not recovered to the protocol-required level. 4. Active central nervous system (CNS) metastases or suspected or confirmed leptomeningeal disease. Participants with treated and stable brain metastases may be eligible. 5. Recent thromboembolic event or clinically significant cardiovascular disease. 6. Active or uncontrolled infection, including active viral hepatitis, unless protocol-defined eligibility criteria are met. 7. Known HIV infection or AIDS-related illness unless protocol-defined eligibility criteria are met. 8. History of or current drug-induced interstitial lung disease/pneumonitis, suspected interstitial lung disease (ILD)/pneumonitis, or other severe or uncontrolled chronic pulmonary disease. 9. Another malignancy within the previous 3 years, except certain malignancies with a low risk of recurrence. 10. Recent systemic corticosteroid therapy or live attenuated vaccination, except as permitted by the protocol. 11. Known hypersensitivity to DEM301 or its ingredients, or any serious medical, psychiatric, or other condition that, in the Investigator's opinion, could affect participant safety, study participation, or interpretation of study results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose-Limiting Toxicities (DLTs) | 21 Days | Incidence of DLTs in DLT-evaluable participants enrolled in Dose Escalation. |
| Incidence of Adverse Events (AEs) | From first dose through 30 days after the last dose, up to approximately 24 months | Incidence of AEs, including events requiring dose interruption or discontinuation, in participants enrolled in Dose Escalation and Dose Expansion. |
| Incidence of Serious Adverse Events (SAEs) | From signing informed consent through 30 days after the last dose, up to approximately 24 months | Incidence of SAEs in participants enrolled in Dose Escalation and Dose Expansion. Related SAEs occurring after the End of Treatment visit will also be reported according to the protocol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of DEM301, if Applicable | At completion of Dose Escalation, approximately 12 months | The MTD of DEM301, if applicable, will be determined based on available Dose Escalation data. |
| Recommended Dose(s) for Expansion (RDEs) of DEM301 | At completion of Dose Escalation, approximately 12 months | One or more recommended doses for expansion will be selected based on available Dose Escalation data. |
| Objective Response Rate (ORR) at 12 Weeks | 12 weeks | ORR at 12 weeks will be assessed according to RECIST v1.1 in response-evaluable participants in Dose Escalation and Dose Expansion. |
| Duration of Response (DoR) | Up to approximately 24 months | Duration of response will be evaluated according to RECIST v1.1 in participants with a documented response in Dose Escalation and Dose Expansion. |
| Disease Control Rate (DCR) at 12 Weeks | 12 Weeks | DCR at 12 weeks will be assessed according to RECIST v1.1 in response-evaluable participants in Dose Escalation and Dose Expansion. |
| Progression-Free Survival (PFS) at 12 Weeks | 12 Weeks | PFS at 12 weeks will be evaluated in response-evaluable participants in Dose Escalation and Dose Expansion. |
| Overall Survival (OS) at 24 Weeks | 24 Weeks | OS at 24 weeks will be evaluated in participants in Dose Escalation and Dose Expansion. |
| Area Under the Concentration-Time Curve (AUC) of DEM301 and Protocol-Specified Analytes | At protocol-specified pharmacokinetics (PK) sampling time points, up to approximately 24 months | AUC will be characterized for DEM301 and protocol-specified analytes in participants in Dose Escalation and Dose Expansion. |
| Terminal Elimination Half-Life (t½) of DEM301 and Protocol-Specified Analytes | At protocol-specified PK sampling time points, up to approximately 24 months | Terminal elimination half-life will be characterized for DEM301 and protocol-specified analytes in participants in Dose Escalation and Dose Expansion. |
| Maximum Concentration (Cmax) of DEM301 and Protocol-Specified Analytes | At protocol-specified PK sampling time points, up to approximately 24 months | Maximum concentration will be characterized for DEM301 and protocol-specified analytes in participants in Dose Escalation and Dose Expansion. |
| Immunogenicity of DEM301 | At protocol-specified PK sampling time points, up to approximately 24 months | The presence of anti-drug antibodies and neutralizing antibodies will be evaluated in participants in Dose Escalation and Dose Expansion. |
Contacts
CONTACTDEM301 Study Team
Outcome results
None listed