KS014 in Advanced Solid Tumors That Express HER2

• Drug: IKS014

Inclusion Criteria:

• HER2 positive solid tumors with expression defined as IHC3+, IHC2+/ISH+, or low HER2 expression defined as IHC2+ (ISH-) or IHC1+ (ISH- /+ or untested).
• Participants with HR positive BC must have received prior treatment with a CDK4/6 inhibitor, in countries where this is standard therapy.
• Plateletssmall disc-shaped blood cells that clump together to form clots to stop bleeding ≥ 75,000 /mcL
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count ≥ 1000/mcL
• No administration of granulocyte colony-stimulating factor (G-CSF) is allowed within 2 weeks prior to first study drug administration
• Creatinine clearance > 45/mL/min (using the Cockcroft-Gault equation)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 3 x institutional upper limit of normal (ULN) ≤ 5 x ULN if liver metastases present
• Total bilirubin ≤ 1.5 x ULN if no liver metastases or < 3 x ULN with Gilbert’s Syndrome or liver metastases at baseline
• Albumin > 2.5 g/dL
• Prothrombin time or international normalized ratio (INR) and either partial thromboplastin time (PTT) or activated (a) PTT ≤ 1.5 x ULN, ≤ 3 x institutional ULN if anticoagulated.
• Must have adequate treatment washout period before trial treatment, defined as: Major surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence (≥ 4 weeks) and radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells (≥ 3 weeks; in case of palliative radiation ≥ 2 weeks)
• Eastern Cooperative Oncologythe study, diagnosis and treatment of cancer Group (ECOG) performance status (PS) of 0 or 1 (or equivalent Karnofsky PS)
• Part 2 Dose Expansion Cohorts May Include:
  1. Advanced or metastatic BC that is confirmed HER2-positive defined as IHC 3+ or IHC 2+ and evidence of HER2 amplification by ISH, as per ASCO-CAP and previously treated with at least two HER2 directed treatments.
  2. Advanced or metastatic BC that has low HER2 expression defined as IHC2+ (ISH-) or IHC1+ (ISH-/+ or untested) and previously treated with at least 1 prior line of therapy which may include chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells and/or a HER2 directed ADC.
  3. Advanced or metastatic GC or GEJ cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs that is confirmed HER2-positive defined as IHC 3+ or IHC 2+ and evidence of HER2 amplification by ISH as per ASCO-CAP and previously treated with at least 1 prior line of therapy, which may include chemotherapy and/or a HER2 directed ADC.
  4. Advanced or metastatic GC or GEJ cancer that has low HER2 expression defined as IHC2+ (ISH-) or IHC1+ (ISH-/+ or untested) and has been previously treated with at least one prior line of therapy.
  5. Advanced or metastatic solid tumor that has any degree of HER2 expression (HER2 IHC3+, IHC2+, IHC1+ or ISH+) or a known activating HER2 mutation and has been treated with standard of care therapy relevant to the disease.