A Phase 1 Study of DEM301 in Participants With Metastatic Colorectal Cancer

A Phase 1, Open-Label, Two-Part (Dose Escalation and Expansion) Study of DEM301 in Participants With Select Advanced Solid Tumors

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.

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.

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.