Clinical Trials List
Protocol NumberM16-289
NCT Number(ClinicalTrials.gov Identfier)NCT03061812
2017-08-24 - 2020-12-31
Phase III
Terminated4
ICD-9162.9
Malignant neoplasm of bronchus and lung, unspecified
A Randomized, Open-Label, Multicenter, Phase 3 Study of Rovalpituzumab Tesirine Compared With Topotecan for Subjects With Advanced or Metastatic DLL3high Small Cell Lung Cancer (SCLC) Who Have First Disease Progression During or Following Front-Line Platinum-Based Chemotherapy (TAHOE)
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Trial Applicant
AbbVie
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Sponsor
AbbVie
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Wei-Pang Chung Division of Hematology & Oncology
- Yu-Min Yeh Division of Hematology & Oncology
- Seu-Chun Yang Division of Hematology & Oncology
- Shang-Yin Wu Division of Hematology & Oncology
- Jui-Hung Tsai Division of Hematology & Oncology
- Wen-Pin Su Division of Hematology & Oncology
- Chien-Chung Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
- JENG-SEN TSENG Division of Thoracic Medicine
- 陳焜結 Division of Thoracic Medicine
- KUO-HSUAN HSU Division of Thoracic Medicine
- TSUNG -YING YANG Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 張平穎 Division of Hematology & Oncology
- 葉人華 Division of Hematology & Oncology
- 陳宇欽 Division of Hematology & Oncology
- 吳宜穎 Division of Hematology & Oncology
- 彭萬誠 Division of Hematology & Oncology
- 戴明燊 Division of Hematology & Oncology
- 陳佳宏 Division of Hematology & Oncology
- 黃子權 Division of Hematology & Oncology
- 簡志峰 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Chong-Jen Yu Division of Thoracic Medicine
- CHAO-CHI HO CHAO-CHI HO Division of Thoracic Medicine
- 許嘉林 Division of Thoracic Medicine
- 林宗哲 Division of Hematology & Oncology
- JIN-YUAN SHIH Division of Thoracic Medicine
- 廖唯昱 Division of Thoracic Medicine
- 蔡子修 Division of Thoracic Medicine
- 吳尚俊 Division of Thoracic Medicine
- 陳冠宇 Division of Thoracic Medicine
- Jih-Hsiang Lee Division of Thoracic Medicine
- 廖斌志 Division of Hematology & Oncology
- 林育麟 Division of Hematology & Oncology
- Chia-Chi Lin Division of Hematology & Oncology
- 楊景堯 Division of Thoracic Medicine
- 徐偉勛 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Small Cell Lung Cancer (SCLC)
Objectives
Primary
To assess if treatment with rovalpituzumab tesirine improves objective response rate (ORR) and
overall survival (OS) compared to topotecan in subjects with advanced or metastatic DLL3high
SCLC who have first disease progression during or following front-line platinum based
chemotherapy.
Secondary
To assess if the treatment with rovalpituzumab tesirine improves progression free survival
(PFS) compared to topotecan in subjects with advanced or metastatic DLL3high SCLC who have
first disease progression during or following front-line platinum based chemotherapy.
To compare the duration of objective response between two arms.
To assess the effect on patient reported outcomes (i.e., health-related quality of life and
symptom assessment) due to treatment with rovalpituzumab tesirine compared to topotecan in
subjects with advanced or metastatic DLL3high SCLC who have first disease progression during
or following front-line platinum based chemotherapy
Test Drug
Rovalpituzumab Tesirine(Rova-T)
Active Ingredient
Rovalpituzumab Tesirine
Dosage Form
injection
Dosage
30mg/10ml
Endpoints
Efficacy:
Overall Survival (OS): After the End of treatment, survival information will be collected at
approximately 6-week intervals (or as requested by sponsor to support data analysis) continuing until the
endpoint of death, the subject becomes lost to follow-up, or AbbVie terminates the study.
Objective Response Rate (ORR): will be derived per RECIST version 1.1. Radiographic tumor
assessments for response will be conducted by CT scanning at baseline, every 6 weeks for 30 weeks,
then every 9 weeks until progression or death.
Progression-Free Survival (PFS): will be derived according to radiographic progression per RECIST
version 1.1 or death. Radiographic tumor assessments for response will be conducted by CT scanning.
Patient-Reported Outcomes (PRO): health-related quality of life (HRQOL) and symptom assessment
will be assessed at baseline, during the treatment cycle, at the end of treatment visit and every 6 weeks
thereafter until disease progression or initiation of new anti-cancer therapy via the European
Organization for Research and Treatment of Cancer QLQ-C15-PAL (EORTC QLQ-C15-PAL), EORTC
QLQ-LC13, and EuroQoL Five Dimensions Questionnaire (EQ-5D-5L) questionnaires.
Safety:
Adverse events, laboratory profiles, physical examinations and vital signs will be assessed throughout
the study.
Overall Survival (OS): After the End of treatment, survival information will be collected at
approximately 6-week intervals (or as requested by sponsor to support data analysis) continuing until the
endpoint of death, the subject becomes lost to follow-up, or AbbVie terminates the study.
Objective Response Rate (ORR): will be derived per RECIST version 1.1. Radiographic tumor
assessments for response will be conducted by CT scanning at baseline, every 6 weeks for 30 weeks,
then every 9 weeks until progression or death.
Progression-Free Survival (PFS): will be derived according to radiographic progression per RECIST
version 1.1 or death. Radiographic tumor assessments for response will be conducted by CT scanning.
Patient-Reported Outcomes (PRO): health-related quality of life (HRQOL) and symptom assessment
will be assessed at baseline, during the treatment cycle, at the end of treatment visit and every 6 weeks
thereafter until disease progression or initiation of new anti-cancer therapy via the European
Organization for Research and Treatment of Cancer QLQ-C15-PAL (EORTC QLQ-C15-PAL), EORTC
QLQ-LC13, and EuroQoL Five Dimensions Questionnaire (EQ-5D-5L) questionnaires.
Safety:
Adverse events, laboratory profiles, physical examinations and vital signs will be assessed throughout
the study.
Inclution Criteria
Main Inclusion:
1. Adult age 18 years or older, who have provided written informed consent.
2. Histologically or cytologically confirmed advanced or metastatic SCLC with documented
first disease progression during or following front-line platinum-based systemic regimen.
3. Tumor must have high DLL3 expression (DLL3high) defined as having ≥ 75% tumor cells staining
positive according to the VENTANA DLL3 (SP347) IHC Assay. Archived or fresh tumor material
can be used for the DLL3 testing.
4. Measurable disease, as defined per Response Evaluation Criteria in Solid Tumors [RECIST]
version 1.1 per the Central Radiographic Assessment Committee (CRAC).
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Subjects with a history of central nervous system (CNS) metastases must have no active CNS
disease, defined as stable or improved clinical status for at least 2 weeks after completion of
definitive treatment (surgical resection, WBRT or stereotactic RT) and prior to randomization, off
or on a stable dose (≤ 10 mg prednisone equivalent) of corticosteroids. No radiographic evidence
of progression of definitively treated CNS disease can be present at the baseline tumor assessment.
7. Recovery to Grade 0 or 1 of any clinically significant toxicity (excluding alopecia) prior to
initiation of study drug administration.
8. Satisfactory laboratory parameters:
a. Absolute neutrophil count (ANC) ≥ 1,500/µL
b. Platelet count ≥ 100,000/µL
c. Hemoglobin ≥ 9.0 g/dL
d. Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for subjects with
Gilbert's disease
e. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN
(≤ 5 × ULN if evidence of hepatic involvement by malignant disease)
f. Calculated creatinine clearance ≥ 40 mL/min by the Cockroft-Gault formula
g. Albumin ≥ 3 g/dL
9. If female, subject must be either postmenopausal as defined as:
Age > 55 years with no menses for 12 or more months without an alternative medical cause.
Age ≤ 55 years with no menses for 12 or more months without an alternative medical cause
AND an FSH level > 40 IU/L.
OR
Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
OR Women of Childbearing Potential (WOCBP) practicing at least one protocol specified method
of birth control, starting at randomization through at least 6 months after the last dose of
investigational product.
If the male subject is sexually active, he must agree, from randomization through at least 6 months
after the last dose of investigational product, to practice the protocol specified contraception.
10. Females of childbearing potential must have a negative serum pregnancy test result at Screening,
and a negative urine pregnancy test at randomization.
Females of non-childbearing potential (either postmenopausal or permanently surgically sterile) at
Screening do not require pregnancy testing.
11. Subject must voluntarily sign and date an informed consent, approved by an Independent Ethics
Committee (IEC/Institutional Review Board (IRB)), prior to the initiation of any screening or
study-specific procedures and should be willing and able to comply with parameters as outlined in
the protocol.
1. Adult age 18 years or older, who have provided written informed consent.
2. Histologically or cytologically confirmed advanced or metastatic SCLC with documented
first disease progression during or following front-line platinum-based systemic regimen.
3. Tumor must have high DLL3 expression (DLL3high) defined as having ≥ 75% tumor cells staining
positive according to the VENTANA DLL3 (SP347) IHC Assay. Archived or fresh tumor material
can be used for the DLL3 testing.
4. Measurable disease, as defined per Response Evaluation Criteria in Solid Tumors [RECIST]
version 1.1 per the Central Radiographic Assessment Committee (CRAC).
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Subjects with a history of central nervous system (CNS) metastases must have no active CNS
disease, defined as stable or improved clinical status for at least 2 weeks after completion of
definitive treatment (surgical resection, WBRT or stereotactic RT) and prior to randomization, off
or on a stable dose (≤ 10 mg prednisone equivalent) of corticosteroids. No radiographic evidence
of progression of definitively treated CNS disease can be present at the baseline tumor assessment.
7. Recovery to Grade 0 or 1 of any clinically significant toxicity (excluding alopecia) prior to
initiation of study drug administration.
8. Satisfactory laboratory parameters:
a. Absolute neutrophil count (ANC) ≥ 1,500/µL
b. Platelet count ≥ 100,000/µL
c. Hemoglobin ≥ 9.0 g/dL
d. Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for subjects with
Gilbert's disease
e. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN
(≤ 5 × ULN if evidence of hepatic involvement by malignant disease)
f. Calculated creatinine clearance ≥ 40 mL/min by the Cockroft-Gault formula
g. Albumin ≥ 3 g/dL
9. If female, subject must be either postmenopausal as defined as:
Age > 55 years with no menses for 12 or more months without an alternative medical cause.
Age ≤ 55 years with no menses for 12 or more months without an alternative medical cause
AND an FSH level > 40 IU/L.
OR
Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
OR Women of Childbearing Potential (WOCBP) practicing at least one protocol specified method
of birth control, starting at randomization through at least 6 months after the last dose of
investigational product.
If the male subject is sexually active, he must agree, from randomization through at least 6 months
after the last dose of investigational product, to practice the protocol specified contraception.
10. Females of childbearing potential must have a negative serum pregnancy test result at Screening,
and a negative urine pregnancy test at randomization.
Females of non-childbearing potential (either postmenopausal or permanently surgically sterile) at
Screening do not require pregnancy testing.
11. Subject must voluntarily sign and date an informed consent, approved by an Independent Ethics
Committee (IEC/Institutional Review Board (IRB)), prior to the initiation of any screening or
study-specific procedures and should be willing and able to comply with parameters as outlined in
the protocol.
Exclusion Criteria
Main Exclusion:
1. Any significant medical condition that, in the opinion of the investigator or Sponsor, may place the
subject at undue risk from the study, including but not necessarily limited to uncontrolled
hypertension and/or diabetes, clinically significant pulmonary disease or neurological disorder
(e.g., seizure disorder active within 6 months).
2. Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable
angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association
(NYHA) Class III – IV within 6 months prior to their first dose of study drug.
3. Known leptomeningeal metastases.
4. Isolated CNS disease progression with no evidence of progression outside of CNS.
5. More than one prior systemic therapy regimen for SCLC (prior systemic maintenance therapy
following front-line platinum based regimen, administered as part of a clinical trial is allowed).
6. Grade 2 or higher pleural or pericardial effusion within 4 weeks of randomization or earlier history
of recurrent Grade 2 or higher pleural or pericardial effusions with ongoing requirement for
pericardiocentesis or thoracentesis.
7. History of capillary leak syndrome within 6 months of randomization.
8. Serious infection within 2 weeks prior to randomization, including any Grade 3 or higher (per
National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE]
version 4.0) viral, bacterial, or fungal infection.
9. Female subject who is pregnant, breastfeeding or is considering becoming pregnant during the
study or for approximately 6 months after the last dose of study drug.
10. Male subject who is considering fathering a child or donating sperm during the study or for
approximately 6 months after the last dose of study drug.
11. Systemic therapy with corticosteroids at > 10 mg/day prednisone equivalent within 1 week prior to
the first dose of study drug for subjects with history of CNS metastases.
12. Subject has a history of active malignancies other than SCLC within the past 2 years prior to study
entry, with the exception of in situ cancer which was curatively treated.
13. Treatment with any of the following within the noted time intervals prior to the first dose of study
drug:
within 2 weeks: small molecule targeted agents with half-life of < 7 days; radiation not
involving the thoracic cavity.
within 4 weeks: chemotherapy; radiation involving the thoracic cavity; small molecule
targeted agents with half-life of ≥ 7 days; monoclonal antibodies, antibody-drug conjugates,
radioimmunoconjugates, or T-cell or other cell-based therapies
14. Prior exposure to a pyrrolobenzodiazepine (PBD)-based drug, or known hypersensitivity to
rovalpituzumab tesirine, or excipient contained in the drug formulation.
15. Prior exposure to topotecan, irinotecan or any other topoisomerase I inhibitors.
16. Participation in a previous study with rovalpituzumab tesirine as an investigational agent.
1. Any significant medical condition that, in the opinion of the investigator or Sponsor, may place the
subject at undue risk from the study, including but not necessarily limited to uncontrolled
hypertension and/or diabetes, clinically significant pulmonary disease or neurological disorder
(e.g., seizure disorder active within 6 months).
2. Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable
angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association
(NYHA) Class III – IV within 6 months prior to their first dose of study drug.
3. Known leptomeningeal metastases.
4. Isolated CNS disease progression with no evidence of progression outside of CNS.
5. More than one prior systemic therapy regimen for SCLC (prior systemic maintenance therapy
following front-line platinum based regimen, administered as part of a clinical trial is allowed).
6. Grade 2 or higher pleural or pericardial effusion within 4 weeks of randomization or earlier history
of recurrent Grade 2 or higher pleural or pericardial effusions with ongoing requirement for
pericardiocentesis or thoracentesis.
7. History of capillary leak syndrome within 6 months of randomization.
8. Serious infection within 2 weeks prior to randomization, including any Grade 3 or higher (per
National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE]
version 4.0) viral, bacterial, or fungal infection.
9. Female subject who is pregnant, breastfeeding or is considering becoming pregnant during the
study or for approximately 6 months after the last dose of study drug.
10. Male subject who is considering fathering a child or donating sperm during the study or for
approximately 6 months after the last dose of study drug.
11. Systemic therapy with corticosteroids at > 10 mg/day prednisone equivalent within 1 week prior to
the first dose of study drug for subjects with history of CNS metastases.
12. Subject has a history of active malignancies other than SCLC within the past 2 years prior to study
entry, with the exception of in situ cancer which was curatively treated.
13. Treatment with any of the following within the noted time intervals prior to the first dose of study
drug:
within 2 weeks: small molecule targeted agents with half-life of < 7 days; radiation not
involving the thoracic cavity.
within 4 weeks: chemotherapy; radiation involving the thoracic cavity; small molecule
targeted agents with half-life of ≥ 7 days; monoclonal antibodies, antibody-drug conjugates,
radioimmunoconjugates, or T-cell or other cell-based therapies
14. Prior exposure to a pyrrolobenzodiazepine (PBD)-based drug, or known hypersensitivity to
rovalpituzumab tesirine, or excipient contained in the drug formulation.
15. Prior exposure to topotecan, irinotecan or any other topoisomerase I inhibitors.
16. Participation in a previous study with rovalpituzumab tesirine as an investigational agent.
The Estimated Number of Participants
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Taiwan
10 participants
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Global
444 participants
