A Phase I/II, Open-Label, Non-Randomized, Multi-Centre First-in-Human Study of CAN016 in Patients with Advanced Solid Tumors

This is a Phase I/II, Open-Label, Non-Randomized, Multi-centre First-in-Human Study.

Phase I:

Accelerated Titration Designs and 3+3 escalation design for MTD and/or RP2D determination.

Phase II:

Once the RP2D is determined, the study will enroll patients into Phase II. Approximately 20~60 patients will be enrolled to evaluate the efficacy of CAN016 in HER2 expression or mutation advanced solid tumors.

Inclusion Criteria:

1. Provide informed consent voluntarily

2. Male or female patients ≥18 years of age.

3. Patients must have a histologically or cytologically confirmed diagnosis of recurrent or metastatic HER2 expression or mutation advanced solid tumor that has failed to or intolerable with standard treatment.

   1. For Phase I dose escalation, patients must have had progression of disease on an HER2 targeted ADC and should be refractory to or intolerant of exiting therapy(ies) known to provide clinical benefit for their condition;
   2. For Phase II, patients with advanced/unresectable or metastatic HER2 positive (IHC 3+, 2+/ISH+) breast cancer, HER2 low/ultralow expression (IHC 1+, 2+/ISH-, IHC 0 with membrane staining) breast cancer and other HER2 expression or mutation advanced solid tumors are eligible. Patients must have had progression of disease on prior HER2 targeted ADC.

4. At least one measurable lesion as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

5. Adequate organ function with 7 days before registration

6. Eastern Cooperative Oncology Group (ECOG) performance status ≤1.

7. LVEF ≥50% by either echocardiogram (ECHO) or multigated acquisition scan (MUGA) within 28 days before registration.

8. Life expectancy of ≥3 months.

Exclusion Criteria

1. Patient has received any anticancer therapy (including chemotherapy, targeted therapy, hormonal therapy, biotherapy, immunotherapy, or other investigational agents.) within 28 days or 5 times of half-lives (whichever is shorter) prior to the first dose of the study treatment or who have not recovered from the side effect of such therapy.
2. Radical radiation therapy (including radiation therapy for over 25% bone marrow) within 4 weeks prior to the first dose of the investigational product or received local palliative radiation therapy for bone metastases within 2 weeks.
3. Patients have autologous transplantation within 3 months.
4. Major surgery or had significant traumatic injury within 60 days prior to the first dose of the investigational product or has not recovered from major side effects.
5. Multiple primary malignancies within 5 years, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease.
6. Any toxicities from prior treatment that have not recovered to baseline or ≤CTCAE Grade 1 before the start of study treatment, with exception of hair loss.