A Phase I-II, First-in-Human Study of SKB264 in Patients with Locally Advanced
Unresectable/Metastatic Solid Tumors who are refractory to Available Standard Therapies.
Patient must have historically documented, incurable, locally advanced or metastatic cancer
that are refractory to standard therapies of one of the following types:
1. Triple negative breast cancer
2. Epithelial ovarian cancer
3. Non-small cell lung cancer
4. Gastric adenocarcinoma
5. Small cell lung cancer
6. Urothelial carcinoma
Inclusion Criteria:
Phase I:
1. Patients must be able to provide documented voluntary informed consent.
2. Male or female patient aged 18-75 years.
3. Histologically documented, incurable, locally advanced or metastatic epithelial origin
malignant cancer , priority to include but not limited to the following tumor types:
- Breast cancer
- Ovarian epithelial cancer
- Non-small cell lung cancer
- Gastric adenocarcinoma
- Small cell lung cancer
- Urothelial cancers
Note: Confirmation of TROP2 expression by immunohistology or other means is not
required, but the Sponsor will request tissue specimens from fresh or archived
materials for determination of TROP2 expression.
4. Measurable disease by CT/MRI during dose escalation.
5. Patients should have an unresectable locally advanced or metastatic solid tumor that
is refractory to standard therapies, or have no standard therapies, or standard
treatment is not applicable at this stage.
6. Granulocyte count ≥ 1.5×109/L, platelet count ≥ 100×109/L, and hemoglobin ≥ 9 g/dL.
7. International normalized ratio (INR) and activated partial thromboplastin time (aPTT)
≤ 1.5×ULN.
8. Serum bilirubin ≤ 1.5 mg/dL (Patients with known Gilbert disease who have serum
bilirubin level ≤ 3 ×ULN may be enrolled)., aspartate aminotransferase (AST), alanine
aminotransferase (ALT), and alkaline phosphatase ≤ 2.5 × upper limit of normal (ULN),
with the exception of patients with hepatic metastases (ALT and AST ≤ 5 × ULN) and
patients with hepatic and/or bone metastases (alkaline phosphatase ≤ 5 × ULN).
9. Creatinine clearance ≥ 50 mL/min calculated by Cockcroft-Gault, Chronic Kidney Disease
Epidemiology Collaboration, or Modification of Diet in Renal Disease formulas. Note
that 24 hour urine collection is not required but is allowed.
10. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
11. For female patients of childbearing potential and male patients with partners of
childbearing potential, agreement (by patient and/or partner) to use a highly
effective form(s) of contraception during study treatment . Female and male patient
treated with SKB264 should continue contraception use for 7 months after the last
dose. Such methods include combined (estrogen and progestogen containing) hormonal
contraception, progestogen-only hormonal contraception associated with inhibition of
ovulation together with another additional barrier method always containing a
spermicide, intrauterine device (IUD), intrauterine hormonereleasing system (IUS),
bilateral tubal occlusion or vasectomized partner (on the understanding that this is
the only one partner during the whole study duration), and sexual abstinence.
- Oral contraception should always be combined with an additional contraceptive
method because of a potential interaction with the study drug. The same rules are
valid for male patients involved in this clinical trial if they have a partner of
childbirth potential. Male patients must always use a condom.
- Women are excluded from birth control if they had had tubal ligation or a
hysterectomy.
12. Patients must have recovered (i.e., improvement to Grade 1 or better) from all acute
toxicities from previous therapy, excluding alopecia and vitiligo.
13. Expected survival ≥ 3 months.
Phase II:
1. Patients must be able to provide documented voluntary informed consent.
2. Male or female patient aged 18-75 years.
3. Histologically documented, incurable, locally advanced or metastatic cancer, priority
to include but not limited to the following tumor types (the sponsor will add or
remove indications based on real-time study results):
- Triple negative breast cancer
- Epithelial ovarian cancer
- Non-small cell lung cancer
- Gastric adenocarcinoma
- Small cell lung cancer
- Urothelial carcinoma
Note: Confirmation of TROP2 expression by immunohistology or other means is not
required, but the Sponsor will request tissue specimens from fresh or archived
materials for determination of Trop-2 expression
4. Measurable disease by CT/MRI.
5. Patients should have an unresectable locally advanced or metastatic solid tumor that
is refractory to standard therapies, or have no standard therapies, or standard
treatment is not applicable at this stage.
6. Granulocyte count ≥ 1.5×109/L, platelet count ≥ 100×109/L, and hemoglobin ≥ 9 g/dL.
7. International normalized ratio (INR) and activated partial thromboplastin time (aPTT)
≤ 1.5×ULN.
8. Serum bilirubin ≤ 1.5 mg/dL (Patients with known Gilbert disease who have serum
bilirubin level ≤ 3 ×ULN may be enrolled)., aspartate aminotransferase (AST), alanine
aminotransferase (ALT), and alkaline phosphatase ≤ 2.5 × upper limit of normal (ULN),
with the exception of patients with hepatic metastases (ALT and AST ≤ 5 × ULN) and
patients with hepatic and/or bone metastases (alkaline phosphatase ≤ 5 × ULN).
9. Creatinine clearance ≥ 50 mL/min calculated by Cockcroft-Gault, Chronic Kidney Disease
Epidemiology Collaboration (CKD-EPI), or Modification of Diet in Renal Disease (MDRD)
formulas. Note that 24 hour urine collection is not required but is allowed.
10. ECOG Performance Status 0 or 1.
11. For female patients of childbearing potential and male patients with partners of
childbearing potential, agreement (by patient and/or partner) to use a highly
effective form(s) of contraception during study treatment. Female and male patient
treated with SKB264 should continue contraception use for 7 months after the last
dose. Such methods include combined (estrogen and progestogen containing) hormonal
contraception, progestogen-only hormonal contraception associated with inhibition of
ovulation together with another additional barrier method always containing a
spermicide, intrauterine device (IUD), intrauterine hormonereleasing system (IUS),
bilateral tubal occlusion or vasectomized partner (on the understanding that this is
the only one partner during the whole study duration), and sexual abstinence.
- Oral contraception should always be combined with an additional contraceptive
method because of a potential interaction with the study drug. The same rules are
valid for male patients involved in this clinical trial if they have a partner of
childbirth potential. Male patients must always use a condom.
- Women are excluded from birth control if they had had tubal ligation or a
hysterectomy.
12. Patients must have recovered (i.e., improvement to Grade 1 or better) from all acute
toxicities from previous therapy, excluding alopecia and vitiligo.
13. Expected survival ≥ 3 months.
Exclusion Criteria:
Phase I:
1. Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure
(New York Heart Association) III or IV, unstable angina pectoris even if medically
controlled, history of myocardial infarction during the last 6 months, serious
arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal
supraventricular tachycardia).
2. Symptomatic brain metastases or any radiation or surgery for brain metastases within 3
months of first infusion of study drug.
3. Subjects with second primary cancers (except for cured in situ non-melanoma skin
cancer and in situ cervical cancer with no relapse in the last 3 years).
4. Require supplemental oxygen for daily activities.
5. Documented Grade ≥ 2 peripheral neuropathy.
6. History of documented severe dry eye syndrome, severe Meibomian gland disease and/or
blepharitis, corneal disease that prevents/delays corneal healing, macular
degeneration.
7. Subjects previously treated with TROP 2 targeted therapies.
8. Any standard cancer therapy (e.g chemotherapy, hormonal therapy, radiotherapy,
immunotherapy, biologic therapy treatment, or therapy with traditional Chinese
medicines approved for anti-tumor treatment, etc.) within 4 weeks or five half-lives,
whichever is shorter, of first infusion of study drug.
9. Any experimental therapy within 4 weeks or five half-lives, whichever is shorter, of
first infusion of study drug.
10. Any major surgical procedure within 4 weeks of first infusion of study drug.
11. Diagnosed active liver disease, including viral or other hepatitis, current or history
of alcoholism, or cirrhosis.
12. Have known prior positive test results or medical history for human immunodeficiency
virus.
13. Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood
pressure ≥ 100 mmHg) or diabetes (HbA1c ≥ 9.0%).
14. Subjects who require use of strong inhibitors or inducers of CYP3A4 at least 14 days
prior to and throughout Study. Use of strong inhibitors or inducers of CYP3A4 is not
allowed in this study. List of representative examples of strong inhibitors or
inducers of CYP3A4 is provided in Appendix III.
15. Pregnancy or lactation.
16. Left ventricular ejection fraction < 45% determined by echocardiogram or multiple
gated acquisition scan.
17. Resting QTc > 480 msec at baseline.
18. Ascites requiring paracentesis ≥1 per week.
19. Symptomatic pleural effusion (< 90% oxygen saturation).
20. Subjects with non-infectious interstitial lung diseases (ILD) or medical history of
pneumonia requiring steroid treatments; severe pulmonary dysfunction caused by lung
diseases.
21. New diagnosed thromboembolic events that requires therapeutic intervention over the
last 6 months (patients with stable control of lower limb deep venous thrombosis are
allowed).
22. The investigator considers other situations that patients are not appropriate to
participate in this trial.
Phase II:
1. Any patient who was treated in the Phase I part of this study.
2. Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure
(New York Heart Association) III or IV, unstable angina pectoris even if medically
controlled, history of myocardial infarction during the last 6 months, serious
arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal
supraventricular tachycardia).
3. Symptomatic brain metastases or any radiation or surgery for brain metastases within 3
months of first infusion of study drug.
4. Subjects with second primary cancers (except for cured in situ non-melanoma skin
cancer and in situ cervical cancer with no relapse in the last 3 years).
5. Require supplemental oxygen for daily activities.
6. Documented Grade ≥ 2 peripheral neuropathy.
7. History of documented severe dry eye syndrome, severe Meibomian gland disease and/or
blepharitis, corneal disease that prevents/delays corneal healing, macular
degeneration.
8. Subjects previously treated with TROP 2 targeted therapies.
9. Any standard cancer therapy (e.g chemotherapy, hormonal therapy, radiotherapy,
immunotherapy, or biologic therapy treatment, or therapy with traditional Chinese
medicines approved for anti-tumor treatment, etc.) within 4 weeks or 5 half-lives,
whichever is shorter, of first infusion of study drug.
10. Any experimental therapy within 4 weeks or 5 half-lives, whichever is shorter, of
first infusion of study drug.
11. Any major surgical procedure within 4 weeks of first infusion of study drug.
12. Diagnosed active liver disease, including viral or other hepatitis, current or history
of alcoholism, or cirrhosis.
13. Have known prior positive test results or medical history for human immunodeficiency
virus.
14. Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood
pressure ≥ 100 mmHg) or diabetes (HbA1c ≥ 9.0%).
15. Subjects who require use of strong inhibitors or inducers of CYP3A4 at least 14 days
prior to and throughout Study. Use of strong inhibitors or inducers of CYP3A4 is not
allowed in this Study. List of representative examples strong inhibitors or inducers
of CYP3A4 is provided in Appendix III.
16. Pregnancy or lactation.
17. Left ventricular ejection fraction < 45% determined by echocardiogram or multiple
gated acquisition scan.
18. Resting QTc > 480 msec at baseline.
19. Ascites requiring paracentesis ≥1 per week.
20. Symptomatic pleural effusion (< 90% oxygen saturation).
21. Subjects with non-infectious interstitial lung diseases (ILD) or medical history of
pneumonia requiring steroid treatments; severe pulmonary dysfunction caused by lung
diseases.
22. New diagnosed thromboembolic events that requires therapeutic intervention over the
last 6 months (patients with stable control of lower limb deep venous thrombosis are
allowed).
23. The investigator considers other situations that patients are not appropriate to
participate in this trial.
