Phase I-II, FIH, TROP2 ADC, Advanced Unresectable/Metastatic Solid Tumors, Refractory to Standard Therapies

Breast Cancer Clinical Trial

— A264  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04152499
• Other study ID #: KL264-01
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 28, 2020
• Est. completion date: July 16, 2026

Study information

• Verified date: June 2024
• Source: Klus Pharma Inc.
• Contact: Study Manager
• Phone: +1 416-471-1960
• Email: gurj[@]kelun.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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/Gastroesophageal junction adenocarcinoma 5. Small cell lung cancer 6. HR+/ HER2-breast cancer 7. Head and neck squamous cell carcinoma 8. Endometrial carcinoma 9. Urothelial carcinoma

Description:

This is an open label, Phase I-II, first in human (FIH) study for SKB264 as monotherapy in patients who have locally advanced unresectable or metastatic solid tumor that is refractory to all standard therapies. TROP2 (trophoblast antigen 2) assessments will not be performed prior to enrollment but it will be assessed retrospectively. Confirmation of TROP2 (trophoblast antigen 2) expression by immunohistology or other means is not required, but the Sponsor will request fresh tumor biopsy or tissue specimens from archived materials for determination of TROP2 (trophoblast antigen 2) expression retrospectively. The patient must be, in the judgment of the investigator, an appropriate candidate for experimental therapy whose tumor is refractory to standard therapies. Patients will receive study drug as a single IV infusion at the prescribed dose level at each administration. Cycles will continue until disease progression or unacceptable toxicity. The study is divided into 2 parts (Phase I and Phase II).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1300
• Est. completion date: July 16, 2026
• Est. primary completion date: August 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Diagnosis and Main Criteria for Inclusion:

Inclusion Criteria:

Patients must meet the following criteria for inclusion into the study:

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 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 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 hormone-releasing 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 years.

3. Histologically or cytologically documented, incurable, locally advanced, recurrent or

metastatic cancer, including the following tumor types:

• Cohort 1: triple negative breast cancer (< 1% expression for estrogen receptor [ER] and progesterone receptor [PR] and HER2 negative)
• Cohort 2: ovarian cancer, fallopian tube cancer, or primary peritoneal cancer
• Cohort 3: non-small cell lung cancer
• Cohort 4: gastric adenocarcinoma or gastroesophageal junction adenocarcinoma (HER2 negative)
• Cohort 6: HR+/ HER2- breast cancer (=1% expression for ER and/or PR and HER2 negative)
• Cohort 7: Head and neck squamous cell carcinoma (including primary tumor location of oropharynx, oral cavity, hypopharynx, or larynx. Other primary tumor sites of HNSCC are not eligible)
• Cohort 8: Endometrial carcinoma (including carcinosarcoma, but excluding sarcoma and neuroendocrine endometrial carcinoma)
• Cohort 9: Urothelial carcinoma (including urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra, patients with mixed histology are eligible provided urothelial component > 50% and plasmacytoid component<10%, patients whose tumors contain any neuroendocrine component are not eligible)
• Cohort 10: Cervical cancer (including squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix) Note: Evaluation of TROP-2 expression is required.

4. Measurable disease by CT/MRI.

5. Patients should have an unresectable locally advanced or metastatic solid tumor that is refractory to standard therapies.

6. Neutrophil 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 ×ULN (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 = 30 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 6 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 hormone-releasing 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. Note: Subjects with endocrine AE of any grade are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.

13. Expected survival = 3 months. Exclusion Criteria: Patients that meet the following criteria will be excluded from entry into the study:

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 1 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. Subjects with known meningeal metastases, brainstem metastases, spinal cord metastases and/or compression, or other active CNS metastases.

4. Patients with active 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, or other malignant cancers that have been cured and no evidence of recurrence).

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. Patients previously treated with TROP 2 targeted therapies at any time for early stage or metastatic disease.

9. 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 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 of 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 QTcF > 480 msec at baseline.

19. Ascites requiring paracentesis >1 per week.

20. Symptomatic pleural effusion (< 90% oxygen saturation).

21. History of interstitial lung diseases (ILD) or non-infectious pneumonitis 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. Known allergic to any components of SKB264, including excipients (including polysorbate-20); or history of severe hypersensitivity to another biologic therapy.

24. The investigator considers other situations that patients are not appropriate to participate in this trial.

Related Conditions & MeSH terms

• Adenocarcinoma
• Breast Cancer
• Carcinoma
• Carcinoma, Ovarian Epithelial
• Endometrial Carcinoma
• Endometrial Neoplasms
• Epithelial Ovarian Cancer
• Gastric Adenocarcinoma
• Gastroesophageal Junction Adenocarcinoma
• Head and Neck Squamous Cell Carcinoma
• Lung Neoplasms
• Non-Small Cell Lung Cancer
• Small Cell Lung Carcinoma
• Small-Cell Lung Cancer
• Squamous Cell Carcinoma of Head and Neck
• Urothelial Carcinoma

Intervention

Drug:
• SKB264
SKB264 is an Antibody Drug Conjugate (ADC) targeting TROP2 expressing cancer cells.

Locations

Country	Name	City	State
Canada	MUHC,Glen - Women's Health Research Unit	Montreal	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	Sunnybrook Research Institute	Toronto	Ontario
China	Anyang City Cancer Hospital	Anyang	Henan
China	Beijing Cancer Hospital	Beijing	Beijing
China	Beijing Cancer Hospital	Beijing	Beijing
China	Beijing Chao-Yang Hospital, Capital Medical University	Beijing	Beijing
China	Beijing Obstetrics and Gynecology Hospital, Capital Medical University	Beijing	Beijing
China	Beijing Tongren Hospital, Capital Medical University	Beijing	Beijing
China	Chinese PLA General Hospital (301 Hospital)	Beijing	Beijing
China	Peking University Third Hospital	Beijing	Beijing
China	The First Affiliated Hospital of Bengbu Medical University	Bengbu	Anhui
China	Affiliated Hospital of Binzhou Medical College	Binzhou	Shandong
China	First Hospital of Jilin University	Changchun	Jilin
China	Jilin Cancer Hospital	Changchun	Jilin
China	Hunan Cancer Hospital	Changsha	Hunan
China	Hunan Cancer Hospital	Changsha	Hunan
China	Hunan Cancer Hospital	Changsha	Hunan
China	Hunan Cancer Hospital	Changsha	Hunan
China	Hunan Cancer Hospital	Changsha	Hunan
China	Hunan Cancer Hospital	Changsha	Hunan
China	Hunan Cancer Hospital	Changsha	Hunan
China	Hunan Cancer Hospital	Changsha	Hunan
China	The Second Xiangya Hospital of Central South University	Changsha	Hunan
China	Xiangya Hospital Central South University	Changsha	Hunan
China	Xiangya Hospital of Central South University	Changsha	Hunan
China	Sichuan Cancer Hospital	Chengdu	Sichuan
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	Chongqing University Cancer Hospital	Chongqing	Chongqing
China	Chongqing University Cancer Hospital	Chongqing	Chongqing
China	Chongqing University Cancer Hosptital	Chongqing	Chongqing
China	The Second Hospital of Dalian Medical University	Dalian	Liaoning
China	900TH Hospital of Joint Logistics Support Force	Fuzhou	Fujian
China	Fujian Cancer Hospital	Fuzhou	Fujian
China	Fujian Cancer Hospital	Fuzhou	Fujian
China	Fujian Cancer Hospital	Fuzhou	Fujian
China	Fujian Medical University Uion Hospital	Fuzhou	Fujian
China	Affiliated Hospital of Guangdong Medical University	Guangzhou	Guangdong
China	Guangdong Provincial People's Hospital	Guangzhou	Guangdong
China	Sun Yat-Sen Memorial Hospital , Sun Yat-sen University	Guangzhou	Guangdong
China	Sun Yat-sen Memorial Hospital, Sun Yat-sen University	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer prevention Center	Guangzhou	Guangdong
China	The Second Affiliated Hospital of Guilin Medical University	Guilin	Guangxi
China	Hainan General Hospital	Haikou	Hainan
China	The First Affiliated Hospital of Hainan Medical University	Haikou	Hainan
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Zhejiang University School of Medical Sir Run Run Shaw Hospital	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Anhui Cancer Hospital	Hefei	Anhui
China	AnHui Provincial Cancer Hospital	Hefei	Anhui
China	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	The First Affiliated Hospital of USTC Anhui Provincial Hospital	Hefei	Anhui
China	The Second Hospital of Anhui Medical University	Hefei	Anhui
China	The Second Hospital of anhui medical University	Hefei	Anhui
China	Jinan Central Hospital	Jinan	Shandong
China	Shandong Cancer Hospital	Jinan	Shandong
China	Shandong Cancer Hospital	Jinan	Shandong
China	Affiliated Hospital of Jining Medical College	Jining	Shandong
China	The First Hospital of Lanzhou University	Lanzhou	Gansu
China	The first people's hospital of Lianyungang	Lianyungang	Jiangsu
China	Linyi Cancer Hospital	Linyi	Shandong
China	The First Affiliated Hospital of Henan University of Science and Technology	Luoyang	Henan
China	Jiangxi Cancer Hospital	Nanchang	Jiangxi
China	Jiangxi Cancer Hospital	Nanchang	Jiangxi
China	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	The First Affiliated Hospital of nanchang University	Nanchang	Jiangxi
China	The First Affiliated Hospital of nanchang University	Nanchang	Jiangxi
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Nanjing Drum Tower Hospital	Nanjing	Jiangsu
China	Guangxi Medical University Cancer Center	Nanning	Guangxi
China	Nanyang Center Hospital	Nanyang	Henan
China	Neijiang Second People's Hospital	Neijiang	Sichuan
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Obstetrics&Gynecology Hospital of Fudan University	Shanghai	Shanghai
China	Shanghai East Hospital	Shanghai	Shanghai
China	Shanghai General Hospital	Shanghai	Shanghai
China	Zhongshan Hospital, Fudan University	Shanghai	Shanghai
China	Liaoning Cancer Hospital	Shenyang	Liaoning
China	Shengjing Hospital of China Medical University	Shenyang	Liaoning
China	The First Hospital of China Medical University	Shenyang	Liaoning
China	The Fourth Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Shanxi Cancer Hospital	Taiyuan	Shanxi
China	Shanxi Provincial Cancer Hospital	Taiyuan	Shanxi
China	Taizhou Hospital of Zhejiang Province	Taizhou	Zhejiang
China	The Second Hospital of Tianjin Medical University	Tianjin	Tianjin
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin
China	Weifang People's Hospital	Weifang	Shandong
China	Hubei Cancer Hospital	Wuhan	Hubei
China	Hubei Cancer Hospital	Wuhan	Hubei
China	Hubei Cancer Hospital	Wuhan	Hubei
China	Hubei Cancer Hospital	Wuhan	Hubei
China	Hubei Cancer Hospital	Wuhan	Hubei
China	Tongji Hospital Tongji Medical College Huazhong University Of Science And Technology	Wuhan	Hubei
China	Union Hospital Tongji Medical College Huazhong University Of Science And Technology	Wuhan	Hubei
China	Wuhan Union Hospital of China	Wuhan	Hubei
China	Wuhan Union Hospital of China	Wuhan	Hubei
China	Zhongnan Hospital of Wuhan University	Wuhan	Hubei
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi
China	The First Affiliated Hospital Of Xiamen University	Xiamen	Fujian
China	Xiangyang Central Hospital	Xiangyang	Hubei
China	The First Affiliated Hospital of Xinxiang Medical College	Xinxiang	Henan
China	Xuzhou Central Hospital	Xuzhou	Jiangsu
China	Yibin Second People's Hospital	Yibin	Sichuan
China	Henan Cancer Hospital	Zhengzhou	Henan
China	Henan Cancer Hospital	Zhengzhou	Henan
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan
China	Zhengzhou Central Hospital	Zhengzhou	Henan
France	CHU d'Amiens	Amiens	Somme
France	Institut de Cancérologie de l'Ouest	Angers	Maine-et-Loire
France	Centre Georges Francois Leclerc - service d'oncologie médicale	Dijon	Côte-d'Or
France	Centre Hospitalier Lyon Sud	Pierre-Bénite	Rhône-Alpes
France	Hopital Bégin	Saint-Mandé	Val-de-Marne
France	Institut Gustave Roussy	Villejuif	Val-de-Marne
Hungary	Orszagos Onkologiai Intezet	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont	Debrecen
Hungary	Zala Megyei Szent Rafael Korhaz - Onkologiai Osztaly	Zalaegerszeg	Zala
Italy	ASST Spedali Civili di Brescia	Brescia
Italy	Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori IRCCS	Meldola	Forli-Cesena
Italy	Ospedale San Gerardo, ASST di Monza, IRCCS	Monza	Monza E Brianza
Italy	PU A. Gemelli, Università Cattolica del Sacro Cuore	Roma
Italy	AOU Senese, Policlinico Santa Maria alle Scotte	Siena
Korea, Republic of	Inje University Haeundae Paik Hospital	Busan
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	CHA Bundang Medical Center, CHA University	Gyeonggi-do
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Gangnam Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	Ajou University Hospital	Suwon
Spain	Hospital Clinic De Barcelona	Barcelona	Catalunya
Spain	Hospital Universitari Vall D Hebron	Barcelona
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	University Hospital Virgen del Rocío S.L.	Sevilla	Andalucía
Turkey	Ankara Bilkent Sehir Hastanesi Tibbi Onkoloji Klinigi	Ankara
Turkey	Ankara Liv Hospital Tibbi Onkoloji	Ankara
Turkey	Memorial Saglik Grubu - Memorial Ankara Hastanesi	Ankara
Turkey	Ege University Medical Faculty	Bornova	Izmir
Turkey	Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi Tibbi Onkoloji	Istanbul
Turkey	Istanbul University Cerrahpasa Medical Faculty	Istanbul
Turkey	Kocaeli University Research and Practice Hospital	Kocaeli
Turkey	Akdeniz University Medical Faculty	Konyaalti	Antalya
Turkey	Gazi University Medical Faculty	Yenimahalle	Ankara
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Los Angeles Hematology Oncology Medical Group	Glendale	California
United States	START MidWest	Grand Rapids	Michigan
United States	MD Anderson Cancer Center	Houston	Texas
United States	Florida Cancer Specialists & Research Institute	Lake Mary	Florida
United States	University of California Los Angeles	Los Angeles	California
United States	The University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	BRCR Medical Center, Inc	Plantation	Florida
United States	Providence Cancer Institute, Franz Clinic	Portland	Oregon
United States	Florida Cancer Specialists and Research Institute	Sarasota	Florida
United States	Willis-Knighton Medical Center	Shreveport	Louisiana
United States	Oklahoma Cancer Specialists and Research Institute, LLC	Tulsa	Oklahoma
United States	Georgetown University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Klus Pharma Inc.

Countries where clinical trial is conducted

United States,  Canada,  China,  France,  Hungary,  Italy,  Korea, Republic of,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase I: Maximum Tolerated Dose (MTD) and Recommended Doses for Expansion (RDEs)	To determine the maximum tolerated dose (MTD) and/or recommended doses for expansion (RDEs). RDEs will not exceed MTD.	Assess up to 12 months
Primary	Phase II: Objective Response Rate (ORR)	To evaluate the objective response rate (ORR) [Complete Response (CR) + Partial Response (PR)] of SKB264 when administered intravenously (IV) as monotherapy at the RDEs to patients with metastatic or locally advanced unresectable tumors.	From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months
Secondary	Phase I: Dose Limiting Toxicities (DLTs)	To determine the dose limiting toxicities (DLTs) of SKB264 when administered IV twice (on Days 1 and 15) every 2 weeks in 4 weeks (28 days) cycles as monotherapy to patients with metastatic or locally advanced unresectable tumors.	Day 28 days after first infusion of study drug
Secondary	Phase I: Overall safety and tolerability profile	Percentage of patients with adverse events (AEs), serious adverse events (SAEs), AEs with Grade = 3 per NCI CTCAE v5.0, adverse events of Special Interest (AESI) and AEs related to study drug.	from the date of informed consent until 30 days after last infusion of study drug or begin a new anti cancer therapy, whichever occurs first
Secondary	Phase I: Preliminary efficacy based on ORR (Objective Response Rate)	ORR (Objective Response Rate) as determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, which will be complete response (CR) + partial response (PR)	From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, approximately 12 months
Secondary	Phase I: Preliminary efficacy based on DOR(Duration of Response)	To evaluate preliminary efficacy in patients treated with SKB264 as monotherapy based on DOR(Duration of Response).	From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, approximately 12 months
Secondary	Phase I: Preliminary efficacy based on PFS(Progression-Free Survival)	To evaluate preliminary efficacy in patients treated with SKB264 as monotherapy based on PFS(Progression-Free Survival).	From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, approximately 12 months
Secondary	Phase I: Preliminary efficacy based on OS(Overall Survival)	To evaluate preliminary efficacy in patients treated with SKB264 as monotherapy based on OS(Overall Survival)	From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, approximately 12 months
Secondary	Phase I: Percentage of patients with ADA formation to SKB264.	To assess the incidence of anti-drug antibody (ADA) formation to SKB264.	From Cycle 1 to Cycle 6 and End of Treatment(EOT), approximately 12 months
Secondary	Phase I: PK parameters for SKB264-ADC, SKB264 TAB, and free KL610023 payload.	To characterize the PK of SKB264-ADC, SKB264 TAB, and free KL610023 payload, such as Cmax	From Cycle 1 to Cycle 6 and End of Treatment(EOT), approximately 12 months
Secondary	Phase II: Overall safety and tolerability profile	Percentage of patients with adverse events (AEs), serious adverse events (SAEs), AEs with Grade = 3 per NCI CTCAE v5.0, adverse events of Special Interest (AESI) and AEs related to study drug.	from the date of informed consent until 30 days after last infusion of study drug or begin a new anti cancer therapy, whichever occurs first
Secondary	Phase II: Efficacy based on DOR (Duration of Response)	To evaluate efficacy in patients treated with SKB264 as monotherapy based on DOR(Duration of Response)	From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, approximately 12 months.
Secondary	Phase II: Efficacy based on PFS (Progression-Free Survival)	To evaluate efficacy in patients treated with SKB264 as monotherapy based on PFS (Progression-Free Survival)	From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, approximately 12 months.
Secondary	Phase II: Efficacy based on OS (Overall Survival)	To evaluate efficacy in patients treated with SKB264 as monotherapy based on OS (Overall Survival)	From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, approximately 12 months.
Secondary	Phase II: Percentage of patients with ADA formation to SKB264.	To obtain Percentage of patients with ADA formation to SKB264.	From Cycle 1 to Cycle 6 and End of Treatment(EOT), approximately 12 months
Secondary	Phase II: PK parameters for SKB264-ADC, SKB264 TAB, and free KL610023 payload	To characterize the PK of SKB264-ADC, SKB264 TAB, and free KL610023 payload, such as half life	From Cycle 1 to Cycle 6 and End of Treatment(EOT), approximately 12 months
Secondary	Phase II: Levels of TROP2 expression in tumor tissue	To assess levels of TROP2 expression in tumor tissue and correlation of those levels with responses and toxicity.	Screening and End of Treatment(EOT), approximately 12 months