Study of DF1001 in Patients With Advanced Solid Tumors

Prior treatment

• Concurrent anticancer treatment (eg, cytoreductive therapy, radiotherapy \[with the exception of palliative bone directed radiotherapy\], immune therapy, or cytokine therapy except for erythropoietin), major surgery (excluding prior diagnostic biopsy), concurrent systemic therapy with steroids or other immunosuppressive agents, or use of any investigational drug within 28 days or 5 half-lives before the start of study treatment. Note: Patients receiving bisphosphonates are eligible provided treatment was initiated at least 14 days before the first dose of DF1001.
• Receipt of any organ transplantation including autologous or allogeneic stem-cell transplantation.
• Preexisting autoimmune disease (except for patients with vitiligo) needing treatment with systemic immunosuppressive agents for more than 28 days within the last 3 years or clinically relevant immunodeficiencies (eg, dys-gammaglobulinemia or congenital immunodeficiencies), or fever within 7 days of Day 1.
• Persisting toxicity related to prior therapy \> Grade 1 NCI-CTCAE v5.0, however alopecia and sensory neuropathy ≤ Grade 2 is acceptable.
• Known alcohol or drug abuse.

Other illness

• Previous malignant disease other than the target malignancy to be investigated in this study within the last 3 years, with the exception of basal or squamous cell carcinoma of the skin or cervical carcinoma in situ.
• Rapidly progressive disease.
• Active or history of central nervous system (CNS) metastases.
• Significant acute or chronic infections (including historic positive test for human immunodeficiency virus \[HIV\], or active or latent hepatitis B or active hepatitis C tested during the screening window).
• Known severe hypersensitivity reactions to mAbs (≥ Grade 3 NCI-CTCAE v5.0), any history of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of partly controlled asthma).
• Serious cardiac illness
• High-risk uncontrolled arrhythmias ie, tachycardia with a heart rate \> 100/min at rest
• Significant ventricular arrhythmia (ventricular tachycardia) or higher-grade Atrioventricular block (AV-block; second-degree AV-block Type 2 \[Mobitz 2\] or third-degree AV-block)
• Angina pectoris requiring anti-anginal medication
• Clinically significant valvular heart disease
• Poorly controlled hypertension (defined by: systolic \> 180 mm Hg or diastolic \> 100 mm Hg)
• Clinically relevant uncontrolled cardiac risk factors, clinically relevant pulmonary disease or any clinically relevant medical condition in the opinion of the Investigator that may limit participation in this study.
• Severe dyspnea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.
• All other significant diseases (e.g., inflammatory bowel disease), which, in the opinion of the Investigator, might impair the patient's ability to participate
• Any psychiatric condition that would prohibit the understanding or rendering of informed consent.

Lab values

• NYHA III of IV heart failure or systolic dysfunction (LVEF \< 55%)

Other

• Pregnancy or lactation in females during the study.
• Evidence of transmural infarction on ECG
• Legal incapacity or limited legal capacity.
• Incapable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol .

• Signed written informed consent.
• Male or female patients aged ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study entry and an estimated life expectancy of at least 3 months.
• Baseline Left Ventricular Ejection Fraction (LVEF) ≥ 55% measured by echocardiography (preferred) or multigated acquisition (MUGA) scan.
• Adequate hematological function.
• Adequate hepatic function.
• Adequate renal function.
• Effective contraception for women of child bearing potential (WOCBP) patients as defined by World Health Organization (WHO) guidelines for 1 "highly effective" method or 2 "effective" methods.
• Have progression of unresectable locally advanced or metastatic NSCLC after last systemic therapy (as confirmed by investigator) or be intolerant of last systemic therapy.
• Have HER2 overexpression status (IHC 2+ or 3+), or ERBB2 amplification, or HER2 activating mutation
• Have recurrent or progressive disease during or after platinum doublet-based chemotherapy.
• Have received and progressed on or after anti-PD-(L)1 therapy.
• Documented evidence of HR+ metastatic breast cancer
• Documented evidence of HER2- status.
• Disease progression or recurrence after prior therapy.
• Have histologically confirmed HER2+ breast cancer.
• Have received prior treatment with trastuzumab, pertuzumab, ado-trastuzumab emtansine (T-DM1), or trastuzumab deruxtecan (T-DXd).
• Have progression of unresectable locally advanced metastatic breast cancer after last systemic therapy or be intolerant of last systemic therapy.
• Evidence of objective disease, but participation does not require a measurable lesion.
• Locally advanced or metastatic solid tumors, for which no standard therapy exists, or standard therapy has failed.
• HER2 expression by immunohistochemistry and/or erbb2 amplification and/or erbb2 activating mutations.
• Eligible to receive nivolumab per its label for a malignancy of epithelial origin; or
• Have no standard therapy available, or standard therapy has failed, and must not have received nivolumab prior to joining the study.
• HER2 expression by immunohistochemistry and/or ebb2 amplification and/or erbb2 activating mutations must be documented on either archival tissue or fresh tumor biopsy.
• Patients must be eligible for treatment with nab-paclitaxel per its label, or have no standard therapy available, or standard therapy has failed.
• HER2 expression by immunohistochemistry and/or erbb2 amplification and/or erbb2 activating mutations must be documented on either archival tissue or fresh tumor biopsy.
• Fresh tumor biopsy must be obtained during the screening window.
• HER2 expression by immunohistochemistry (IHC).
• Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1.
• Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1.
• Histologically or cytologically documented locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary urothelial, urethra).
• Patients must have received a platinum containing chemotherapy and an anti PD-1 or anti PD-L1 for the treatment of urothelial bladder cancer.
• Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1
• Histologically documented (metastatic or locally advanced) breast cancer.
• Absence of erbb2 amplification by ISH and/or HER2 IHC of 0, 1+, or 2+.
• Patient must have progressed after one line of systemic chemotherapy.
• Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1
• Histologically documented (metastatic or locally advanced) breast cancer.
• Erbb2 amplification by ISH and/or HER2 IHC of 3+, or 2+. If Herceptest score is 2+, ISH results should demonstrate erbb2 amplification.
• Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1.
• Documented history of erbb2 amplification.
• Patients must have received at least one line of an approved or established therapy.
• Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1.
• Advanced (unresectable/recurrent/metastatic) gastric cancer or cancer of the gastro-esophageal junction.
• Tumor must have been declared HER2 positive.
• Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1.
• Advanced (unresectable/recurrent/metastatic) gastric cancer or cancer of the gastro-esophageal junction.
• Tumor must have been declared HER2 low; ISH non-amplified and/or HER2 IHC of 0, 1+ or 2+. If Herceptest score is 0, HER2 must be detected by IHC on at least 1+ of the tumor cells.
• Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1.
• Advanced (unresectable/recurrent/metastatic) esophageal cancer.
• Tumor must have been declared HER2 positive.
• Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1.
• Advanced (unresectable/recurrent/metastatic) esophageal cancer.
• Tumor must have been declared HER2 low; ISH non-amplified and/or HER2 IHC of 0, 1+ or 2+. If Herceptest score is 0, HER2 must be detected by IHC on at least 1+ of the tumor cells.
• Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1.
• Histologically confirmed NSCLC meeting stage criteria for stage IIIB, stage IV, or recurrent disease that has been confirmed to have HER2 expression (at least 1+, however, patients must not carry an erbb2 amplification) via archival or fresh biopsy tissue prior to study enrollment.
• Patients must have recurrent or progressive disease during or after platinum doublet-based chemotherapy.
• Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1.
• Histologically confirmed NSCLC meeting stage criteria for stage IIIB, stage IV, or recurrent disease that has been confirmed to have amplification of erbb2 via archival or fresh biopsy tissue prior to study enrollment.
• Patients must have recurrent or progressive disease during or after platinum doublet-based chemotherapy.