Phase I-II, FIH, TROP2 ADC, Advanced Unresectable/Metastatic Solid Tumors, Refractory to Standard Therapies (KL264-01) (MK-2870-001)

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

A Phase I-II, First-in-Human Study of SKB264 (Sac-TMT; MK-2870) 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
10. Cervical cancer

Study Overview

• Status: Active, not recruiting
• Conditions: Cervical Cancer; Breast Cancer; Non-Small Cell Lung Cancer; Gastric Adenocarcinoma; Epithelial Ovarian Cancer; Head and Neck Squamous Cell Carcinoma; Endometrial Carcinoma; Urothelial Carcinoma; Gastroesophageal Junction Adenocarcinoma; Small-Cell Lung Cancer
• Intervention / Treatment: Drug: SKB264

Detailed 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).

• Study Type: Interventional
• Enrollment (Actual): 1410
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • Princess Margaret Cancer Centre
    • Toronto, Ontario, Canada
      • Sunnybrook Research Institute
  • Quebec
    • Montreal, Quebec, Canada
      • MUHC,Glen - Women's Health Research Unit
• Chile
  • Providencia, Chile
    • Centro de Estudios Clínicos SAGA
  • Santiago, Chile
    • Centro de Investigacion Clinica Bradford Hill
  • Santiago, Chile
    • Pontificia Universidad Catolica de Chile - CICUC
• China
  • Anhui
    • Bengbu, Anhui, China
      • The First Affiliated Hospital of Bengbu Medical University
    • Hefei, Anhui, China
      • The First Affiliated Hospital of Anhui Medical University
    • Hefei, Anhui, China
      • The second hospital of Anhui medical university
    • Hefei, Anhui, China
      • Anhui Provincial Cancer Hospital
    • Hefei, Anhui, China
      • Anhui Cancer Hospital
    • Hefei, Anhui, China
      • The First Affiliated Hospital of USTC Anhui Provincial Hospital
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Beijing Tongren Hospital, Capital Medical University
    • Beijing, Beijing Municipality, China
      • Peking University Third Hospital
    • Beijing, Beijing Municipality, China
      • Beijing Cancer Hospital
    • Beijing, Beijing Municipality, China
      • Beijing Obstetrics and Gynecology Hospital, Capital Medical University
    • Beijing, Beijing Municipality, China
      • Beijing Chao-yang Hospital, Capital Medical University
    • Beijing, Beijing Municipality, China
      • Chinese PLA General Hospital (301 Hospital)
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China
      • Chongqing University Cancer Hospital
    • Chongqing, Chongqing Municipality, China
      • Chongqing University Cancer Hosptital
  • Fujian
    • Fuzhou, Fujian, China
      • Fujian Cancer Hospital
    • Fuzhou, Fujian, China
      • 900TH Hospital of Joint Logistics Support Force
    • Fuzhou, Fujian, China
      • Fujian Medical University Uion Hospital
    • Xiamen, Fujian, China
      • The first affiliated hospital of xiamen university
  • Gansu
    • Lanzhou, Gansu, China
      • The First Hospital of Lanzhou University
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yat-sen University Cancer Center
    • Guangzhou, Guangdong, China
      • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen 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 University Cancer prevention Center
    • Guangzhou, Guangdong, China
      • Affiliated Hospital Of Guangdong Medical University
  • Guangxi
    • Guilin, Guangxi, China
      • The Second Affiliated Hospital of Guilin Medical University
    • Nanning, Guangxi, China
      • Guangxi Medical University Cancer Center
  • Hainan
    • Haikou, Hainan, China
      • Hainan General Hospital
    • Haikou, Hainan, China
      • The First Affiliated Hospital of Hainan Medical University
  • Hebei
    • Shijiazhuang, Hebei, China
      • The Fourth Hospital of Hebei Medical University
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • Harbin medical university cancer hospital
  • Henan
    • Anyang, Henan, China
      • Anyang City Cancer Hospital
    • Luoyang, Henan, China
      • The first affiliated hospital of Henan University of science and technology
    • Nanyang, Henan, China
      • Nanyang Center Hospital
    • Xinxiang, Henan, China
      • The First Affiliated Hospital of Xinxiang Medical College
    • Zhengzhou, Henan, China
      • Henan Cancer Hospital
    • Zhengzhou, Henan, China
      • The first affiliated hospital of Zhengzhou university
    • Zhengzhou, Henan, China
      • Zhengzhou Central Hospital
  • Hubei
    • Wuhan, Hubei, China
      • Hubei Cancer Hospital
    • Wuhan, Hubei, China
      • Zhongnan Hospital of Wuhan University
    • 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
      • Tongji Hospital Tongji Medical College Huazhong University of Science and Technology
    • Xiangyang, Hubei, China
      • Xiangyang Central Hospital
  • Hunan
    • Changsha, Hunan, China
      • Hunan Cancer Hospital
    • Changsha, Hunan, China
      • The second Xiangya hospital of central south university
    • Changsha, Hunan, China
      • Xiangya Hospital of Central South University
    • Changsha, Hunan, China
      • Xiangya Hospital Central South University
  • Jiangsu
    • Lianyungang, Jiangsu, China
      • The First People's Hospital of Lianyungang
    • Nanjing, Jiangsu, China
      • Jiangsu Province Hospital
    • Nanjing, Jiangsu, China
      • Nanjing Drum Tower Hospital
    • Xuzhou, Jiangsu, China
      • Xuzhou Central Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Jiangxi Cancer Hospital
    • Nanchang, Jiangxi, China
      • The First Affiliated Hospital of NanChang University
  • Jilin
    • Changchun, Jilin, China
      • Jilin Cancer Hospital
    • Changchun, Jilin, China
      • First Hospital of Jilin University
  • Liaoning
    • Dalian, Liaoning, China
      • The Second Hospital of Dalian Medical University
    • Shenyang, Liaoning, China
      • Shengjing Hospital Of China Medical University
    • Shenyang, Liaoning, China
      • The First Hospital of China Medical University
    • Shenyang, Liaoning, China
      • Liaoning Cancer Hospital
  • Shaanxi
    • Xi'an, Shaanxi, China
      • The First Affiliated Hospital of Xi'an Jiaotong University
  • Shandong
    • Binzhou, Shandong, China
      • Affiliated Hospital of Binzhou Medical College
    • Jinan, Shandong, China
      • Jinan Central Hospital
    • Jinan, Shandong, China
      • Shandong Cancer Hospital
    • Jining, Shandong, China
      • Affiliated Hospital of Jining Medical College
    • Weifang, Shandong, China
      • Weifang People's Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Fudan University Shanghai Cancer Center
    • Shanghai, Shanghai Municipality, China
      • Shanghai General Hospital
    • Shanghai, Shanghai Municipality, China
      • Shanghai East Hospital
    • Shanghai, Shanghai Municipality, China
      • Zhongshan Hospital, Fudan University
    • Shanghai, Shanghai Municipality, China
      • Obstetrics&Gynecology Hospital of Fudan University
  • Shanxi
    • Taiyuan, Shanxi, China
      • Shanxi Provincial Cancer hospital
    • Taiyuan, Shanxi, China
      • Shanxi Cancer Hospital
  • Sichuan
    • Chengdu, Sichuan, China
      • Sichuan Cancer Hospital
    • Chengdu, Sichuan, China
      • West China Hospital of Sichuan University
    • Neijiang, Sichuan, China
      • Neijiang Second People's Hospital
    • Yibin, Sichuan, China
      • Yibin Second People's Hospital
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China
      • The Second Hospital Of Tianjin Medical University
    • Tianjin, Tianjin Municipality, China
      • Tianjin Medical University Cancer Institute and Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China
      • Zhejiang University School of Medical Sir Run Run Shaw Hospital
    • Taizhou, Zhejiang, China
      • Taizhou Hospital of Zhejiang Province
• South Korea
  • Busan, South Korea
    • Inje University Haeundae Paik Hospital
  • Daegu, South Korea
    • Kyungpook National University Chilgok Hospital
  • Goyang-si, South Korea
    • National Cancer Center
  • Gyeonggi-do, South Korea
    • CHA Bundang Medical Center, CHA University
  • Incheon, South Korea
    • Gachon University Gil Medical Center
  • Seoul, South Korea
    • Asan Medical Center
  • Seoul, South Korea
    • Seoul National University Hospital
  • Seoul, South Korea
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea
    • Gangnam Severance Hospital, Yonsei University Health System
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, South Korea
      • Seoul National University Bundang Hospital
• Turkey (Türkiye)
  • Ankara
    • Yenimahalle, Ankara, Turkey (Türkiye)
      • Gazi University Medical Faculty
• United States
  • California
    • Glendale, California, United States, 91204
      • Los Angeles Hematology Oncology Medical Group
    • Los Angeles, California, United States, 90404
      • University of California Los Angeles
  • Florida
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists and Research Institute
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Start Midwest
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • The University of Oklahoma Health Sciences Center
    • Tulsa, Oklahoma, United States, 74146
      • Oklahoma Cancer Specialists and Research Institute, LLC
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Cancer Institute, Franz Clinic
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I: Dose Escalation; Five dose levels have been selected for evaluation in the Phase I part of the study: 2, 4, 6, 9, and 12 mg/kg of SKB264	Drug: SKB264; SKB264 is an Antibody Drug Conjugate (ADC) targeting TROP2 expressing cancer cells.; Other Names: MK-2870; Sacituzumab Tirumotecan (Sac-TMT)
Experimental: Phase II: Non-Small Cell Lung Cancer; Histologically documented or cytologically, incurable, locally advanced or metastatic cancer	Drug: SKB264; SKB264 is an Antibody Drug Conjugate (ADC) targeting TROP2 expressing cancer cells.; Other Names: MK-2870; Sacituzumab Tirumotecan (Sac-TMT)
Experimental: Phase II: Urothelial carcinoma; Histologically or cytologically documented, incurable, locally advanced or metastatic cancer	Drug: SKB264; SKB264 is an Antibody Drug Conjugate (ADC) targeting TROP2 expressing cancer cells.; Other Names: MK-2870; Sacituzumab Tirumotecan (Sac-TMT)
Experimental: Phase II: Triple Negative Breast Cancer; Histologically documented or cytologically , incurable, locally advanced or metastatic cancer	Drug: SKB264; SKB264 is an Antibody Drug Conjugate (ADC) targeting TROP2 expressing cancer cells.; Other Names: MK-2870; Sacituzumab Tirumotecan (Sac-TMT)
Experimental: Phase II: Epithelial Ovarian Cancer; Histologically documented or cytologically, incurable, locally advanced or metastatic cancer	Drug: SKB264; SKB264 is an Antibody Drug Conjugate (ADC) targeting TROP2 expressing cancer cells.; Other Names: MK-2870; Sacituzumab Tirumotecan (Sac-TMT)
Experimental: Phase II: Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma; Histologically or cytologically documented, incurable, locally advanced or metastatic cancer	Drug: SKB264; SKB264 is an Antibody Drug Conjugate (ADC) targeting TROP2 expressing cancer cells.; Other Names: MK-2870; Sacituzumab Tirumotecan (Sac-TMT)
Experimental: Phase II: Extensive-stage Small Cell Lung Cancer; Histologically documented or cytologically, incurable, locally advanced or metastatic cancer	Drug: SKB264; SKB264 is an Antibody Drug Conjugate (ADC) targeting TROP2 expressing cancer cells.; Other Names: MK-2870; Sacituzumab Tirumotecan (Sac-TMT)
Experimental: Phase II: HR+/ HER2- Breast Cancer; Histologically documented or cytologically, incurable, locally advanced or metastatic cancer	Drug: SKB264; SKB264 is an Antibody Drug Conjugate (ADC) targeting TROP2 expressing cancer cells.; Other Names: MK-2870; Sacituzumab Tirumotecan (Sac-TMT)
Experimental: Phase II: Head and Neck Squamous Cell Carcinoma; Histologically documented or cytologically, incurable, locally advanced or metastatic cancer	Drug: SKB264; SKB264 is an Antibody Drug Conjugate (ADC) targeting TROP2 expressing cancer cells.; Other Names: MK-2870; Sacituzumab Tirumotecan (Sac-TMT)
Experimental: Phase II: Endometrial carcinoma; Histologically documented or cytologically, incurable, locally advanced or metastatic cancer	Drug: SKB264; SKB264 is an Antibody Drug Conjugate (ADC) targeting TROP2 expressing cancer cells.; Other Names: MK-2870; Sacituzumab Tirumotecan (Sac-TMT)
Experimental: Phase II: Cervical Cancer; Histologically or cytologically documented, incurable, locally advanced or metastatic cancer	Drug: SKB264; SKB264 is an Antibody Drug Conjugate (ADC) targeting TROP2 expressing cancer cells.; Other Names: MK-2870; Sacituzumab Tirumotecan (Sac-TMT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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.
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.
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.
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
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
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

Collaborators and Investigators

• Sponsor: Klus Pharma Inc.
• Investigators: Study Chair: Jordi Rodon Ahnert, MD, PhD, M.D. Anderson Cancer Center

Publications and helpful links

General Publications

• Zhao S, Cheng Y, Wang Q, Li X, Liao J, Rodon J, Meng X, Luo Y, Chen Z, Wang W, Yi T, Li Y, Yin Y, Xu H, Yu G, Mi Y, Fan Y, Wainberg ZA, Wang X, Su C, Yu Q, Lai S, Sun L, Zhuang W, Wang X, Yang J, Li Y, Ge J, Li J, Zhang L, Fang W. Sacituzumab tirumotecan in advanced non-small-cell lung cancer with or without EGFR mutations: phase 1/2 and phase 2 trials. Nat Med. 2025 Jun;31(6):1976-1986. doi: 10.1038/s41591-025-03638-2. Epub 2025 Apr 10.
• Ouyang Q, Rodon J, Liang Y, Wu X, Li Q, Song L, Yan M, Tong Z, Liu Y, Wainberg ZA, Wang Y, Geng C, Ulahannan SV, Yu G, Sharma MR, Wang X, Wang JS, Spira A, Zhao W, Sanborn RE, Cheng Y, Wang X, Liu G, Li Y, Ge J, Chartash E, Akala OO, Yin Y. Results of a phase 1/2 study of sacituzumab tirumotecan in patients with unresectable locally advanced or metastatic solid tumors refractory to standard therapies. J Hematol Oncol. 2025 Jun 6;18(1):61. doi: 10.1186/s13045-025-01705-2.

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: October 29, 2019
• First Submitted That Met QC Criteria: November 1, 2019
• First Posted (Actual): November 5, 2019

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: TROP2, ADC
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Respiratory Tract Diseases; Neoplasms by Histologic Type; Uterine Diseases; Genital Diseases, Female; Lung Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Breast Diseases; Carcinoma; Uterine Cervical Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Uterine Neoplasms; Carcinoma, Squamous Cell; Ovarian Neoplasms; Skin and Connective Tissue Diseases; Carcinoma, Ovarian Epithelial; Squamous Cell Carcinoma of Head and Neck; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Uterine Cervical Neoplasms; Small Cell Lung Carcinoma; Endometrial Neoplasms; Carcinoma, Transitional Cell
• Other Study ID Numbers: KL264-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No