Study Comparing Rovalpituzumab Tesirine Versus Topotecan in Subjects With Advanced or Metastatic Small Cell Lung Cancer With High Levels of Delta-like Protein 3 (DLL3) and Who Have First Disease Progression During or Following Front-line Platinum-based Chemotherapy (TAHOE)

Small Cell Lung Cancer Clinical Trial

— TAHOE  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03061812
• Other study ID #: M16-289
• Secondary ID: 2016-003726-17
• Status: Completed
• Phase: Phase 3
• Start date: April 11, 2017
• Est. completion date: February 12, 2020

Study information

• Verified date: February 2021
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this randomized, open-label, 2-arm, phase 3 study is to assess the efficacy, safety and tolerability of rovalpituzumab tesirine versus topotecan in participants with advanced or metastatic SCLC with high levels of DLL3, who have first disease progression during or following front-line platinum-based chemotherapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 444
• Est. completion date: February 12, 2020
• Est. primary completion date: February 12, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participant must have histologically or cytologically confirmed advanced or metastatic Small Cell Lung Cancer (SCLC) with documented first disease progression during or following front-line platinum-based systemic regimen

• Tumor must have high Delta-like protein 3 (DLL3) expression defined as having = 75% tumor cells staining positive according to the VENTANA DLL3 (SP347) IHC Assay.

• Participant must have measurable disease, as defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

• Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

• Participant must have recovery to Grade 0 or 1 of any clinically significant toxicity (excluding alopecia) prior to initiation of study drug administration.

Exclusion Criteria:

• Participant has a 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 Class (NYHA) III - IV within 6 months prior to their first dose of study drug.

• Participant has known leptomeningeal metastases.

• Participant has received more than one prior systemic therapy regimen for SCLC.

• Participant had a serious infection within 2 weeks prior to randomization, including any Grade 3 or higher viral, bacterial, or fungal infection.

• Participant 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.

• Participant had prior exposure to topotecan, irinotecan or any other topoisomerase I inhibitors.

Related Conditions & MeSH terms

• Disease Progression
• Lung Neoplasms
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma

Intervention

Drug:
• Rovalpituzumab tesirine
Powder for solution for infusion in vials.
• Topotecan
Powder or solution for infusion in vials. Topotecan is commercially available as both a powder and solution for infusion. Availability will vary by region.
• Dexamethasone
Oral tablet.

Locations

Country	Name	City	State
Australia	Ballarat Health Service /ID# 158904	Ballarat	Victoria
Australia	Blacktown Hospital /ID# 158907	Blacktown	New South Wales
Australia	The Prince Charles Hospital /ID# 158897	Chermside	Queensland
Australia	Austin Hospital /ID# 158898	Heidelberg	Victoria
Australia	St George Hospital /ID# 158855	Kogarah	New South Wales
Australia	Southern Medical Day Care Ctr /ID# 158853	Wollongong	New South Wales
Belarus	Bobruysk Interdistrict Onco. /ID# 169394	Bobruisk
Belarus	State Institution Republican Scientific Practical Center of Oncology and Medica /ID# 159325	Lesnoy
Belarus	Mogilev Reg. Oncologic dispe /ID# 159326	Mogilev
Belgium	Cliniques universitaires Saint /ID# 158751	Brussels
Belgium	CHU Saint-Pierre /ID# 159521	Bruxelles	Bruxelles-Capitale
Belgium	Grand Hôpital de Charleroi /ID# 158748	Charleroi	Hainaut
Belgium	Hopital de Jolimont /ID# 159755	Haine Saint Paul
Belgium	UZ Leuven /ID# 158752	Leuven
Belgium	CHU de Liege Sart Tilman /ID# 158753	Liege
Belgium	CHU Charleroi (Vesale) /ID# 159756	Montigny-le-tilleul
Brazil	Fundacao Pio XII - Hospital de Cancer de Barretos /ID# 159017	Barretos	Sao Paulo
Brazil	Liga Norte Rio Grandense Cont. /ID# 159015	Natal	Rio Grande Do Norte
Brazil	Associação Hospital Beneficente São Vicente de Paulo - Hospital São Vicente de P /ID# 159668	Passo Fundo	Rio Grande Do Sul
Brazil	Instituto Nacional de Câncer José de Alencar Gomes da Silva (INCA) /ID# 159665	Rio de Janeiro
Brazil	Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto /ID# 159666	Sao Jose Do Rio Preto	Sao Paulo
Bulgaria	UMHAT Sv. Ivan Rilski /ID# 159642	Sofia
Bulgaria	UMHAT Tsaritsa Joanna - ISUL /ID# 159641	Sofia
Canada	Cross Cancer Institute /ID# 159519	Edmonton	Alberta
Canada	Juravinski Cancer Clinic /ID# 159514	Hamilton	Ontario
Canada	Hopital du Sacre Coeur Montreal /ID# 159515	Montreal	Quebec
Canada	CHU de Quebec-Universite Laval /ID# 159093	Quebec City	Quebec
Canada	Cisss Du Bas-Saint-Laurent Hopital Regional de Rimouski /Id# 208931	Rimouski	Quebec
China	Jilin Cancer Hosptial /ID# 204059	Changchun	Jilin
Croatia	Klinicki bolnicki centar Rijeka /ID# 159501	Rijeka	Primorsko-goranska Zupanija
Croatia	Klinicki bolnicki centar Sestre milosrdnice /ID# 158811	Zagreb	Grad Zagreb
Croatia	Klinika za plucne bolesti Jordanovac /ID# 159502	Zagreb	Grad Zagreb
Czechia	Nemocnice Rudolfa a Stefanie /ID# 159652	Benesov
Czechia	Nemocnice Horovice a.s. /ID# 161191	Horovice
Czechia	Krajska nemocnice Liberec a.s. /ID# 159653	Liberec
Czechia	Nemocnice Na Plesi s.r.o. /ID# 161190	Nová Ves pod Pleší	Pribram
Czechia	Thomayerova nemocnice /ID# 159061	Prague	Praha 4
Denmark	Rigshospitalet, Finsen Centre /ID# 158051	Copenhagen
Denmark	Herlev Hospital /ID# 158049	Herlev	Hovedstaden
Denmark	Odense Universitets Hospital /ID# 158050	Odense C	Syddanmark
France	Centre Hosp Intercommunal de Creteil /ID# 162684	Creteil	Val-de-Marne
France	Centre Leon Berard /ID# 160561	Lyon CEDEX 08	Rhone
France	Assis.Publique-Hopital Nord /ID# 160554	Marseille	Provence-Alpes-Cote-d Azur
France	Assistance Publique- Hopitaux /ID# 160552	Paris
France	Hopital Haut-Lévêque /ID# 160558	Pessac CEDEX	Gironde
France	Hospital Pontchaillou /ID# 160555	Rennes
Germany	Evangelische Lungenklinik Berl /ID# 159168	Berlin
Germany	Asklepios Fachkliniken M. Gaut /ID# 158791	Gauting
Germany	Lungen Clinic Grosshansdorf /ID# 158770	Grosshansdorf
Germany	KH Martha-Maria Halle Dolau /ID# 158796	Halle (Saale)	Sachsen-Anhalt
Germany	Thoraxklinik Heidelberg gGmbH /ID# 159169	Heidelberg
Germany	Klinikum Kassel /ID# 158788	Kassel
Germany	Klinik Loewenstein GmbH /ID# 159167	Löwenstein
Greece	General Hospital of Chest Diseases of Athens SOTIRIA /ID# 159165	Athens
Greece	Metropolitan Hospital /ID# 159162	Athens
Greece	University Hospital of Ioannin /ID# 159163	Ioannina
Greece	Euromedica General Clinic /ID# 159161	Thessaloniki
Hungary	Orszagos Koranyi Pulmonologiai Intezet /ID# 158967	Budapest
Hungary	Semmelweis Egyetem /ID# 161197	Budapest
Hungary	Torokbalinti Tudogyogyintezet /ID# 207053	Budapest	Pest
Hungary	Dup_Debreceni Egyetem Klinikai Központ /ID# 161209	Debrecen
Hungary	Veszprem Megyei Tuedoegyogyint /ID# 162607	Farkasgyepu
Hungary	Petz Aladar Megyei Oktato Korh /ID# 158978	Gyor
Hungary	Matrai Gyogyintezet /ID# 158979	Matrahaza
Italy	AUSL 8 Arezzo Ospedale San Don /ID# 160967	Arezzo
Italy	Istituto Europeo di Oncologia /ID# 158942	Milan
Italy	A.O.U. San Luigi Gonzaga /ID# 158945	Orbassano
Italy	Ospedale Santa Maria delle Cro /ID# 158940	Ravenna
Italy	IFO Istituto Nazionale Tumori /ID# 158941	Rome
Japan	Hyogo Cancer Center /ID# 165125	Akashi-shi	Hyogo
Japan	National Cancer Center Hospital /ID# 166768	Chuo-ku	Tokyo
Japan	Kyushu University Hospital /ID# 165723	Fukuoka-shi	Fukuoka
Japan	Himeji Medical Center /ID# 165893	Himeji-shi	Hyogo
Japan	Kansai Medical University Hospital /ID# 165055	Hirakata-shi	Osaka
Japan	Duplicate_Kanazawa University Hospital /ID# 165129	Kanazawa-shi	Ishikawa
Japan	National Cancer Center Hospital East /ID# 165726	Kashiwa-shi	Chiba
Japan	The Cancer Institute Hospital Of JFCR /ID# 166249	Koto-ku	Tokyo
Japan	Kurume University Hospital /ID# 164586	Kurume-shi	Fukuoka
Japan	Matsusaka City Hospital /ID# 166126	Matsusaka-shi MIE
Japan	Aichi Cancer Center Hospital /ID# 164975	Nagoya-shi	Aichi
Japan	Japanese Red Cross Okayama Hospital /ID# 165156	Okayama-shi	Okayama
Japan	Kindai University Hospital /ID# 166394	Osaka-sayama-shi	Osaka
Japan	Osaka City General Hospital /ID# 165717	Osaka-shi	Osaka
Japan	Hokkaido Cancer Center /ID# 165237	Sapporo-shi	Hokkaido
Japan	Sendai Kousei Hospital /ID# 166061	Sendai-shi	Miyagi
Japan	Duplicate_Showa University Hospital /ID# 165574	Shinagawa-ku	Tokyo
Japan	Shizuoka Cancer Center /ID# 166466	Sunto-gun	Shizuoka
Japan	Tokushima University Hospital /ID# 165812	Tokushima-shi	Tokushima
Japan	Wakayama Medical University /ID# 166032	Wakayama-shi	Wakayama
Japan	Kanagawa Cancer Center /ID# 165816	Yokohama
Japan	Kanagawa Cardiovascular and Respiratory Center /ID# 164374	Yokohama-shi	Kanagawa
Japan	Yokohama City University Hospital /ID# 165748	Yokohama-shi	Kanagawa
Korea, Republic of	Dong-A University Hospital /ID# 159296	Busan	Busan Gwang Yeogsi
Korea, Republic of	Chungbuk National University /ID# 159291	Cheongju-si
Korea, Republic of	Kyungpook National University Chilgok Hospital /ID# 159292	Daegu	Seoul Teugbyeolsi
Korea, Republic of	Chonnam National University Hospital /ID# 159294	Gwangju	Jeonranamdo
Korea, Republic of	Yonsei University Health System, Severance Hospital /ID# 159288	Seodaemun-gu	Seoul Teugbyeolsi
Korea, Republic of	CHA Bundang Medical center CHA University /ID# 204416	Seongnam si	Gyeonggido
Korea, Republic of	Asan Medical Center /ID# 159290	Seoul
Korea, Republic of	Korea University Guro Hospital /ID# 159293	Seoul	Seoul Teugbyeolsi
Latvia	Pauls Stradins Clinical /ID# 158713	Riga
Latvia	Riga East Clinical University /ID# 158714	Riga
Mexico	Health Pharma Professional Research S.A de C.V /ID# 160020	Del. Benito Juárez
Mexico	Centro de Investigación Clinica Chapultepec /ID# 161000	Morelia	Michoacan
Netherlands	Universitair Medisch Centrum Groningen /ID# 158088	Groningen
Netherlands	Ziekenhuis St. Jansdal /ID# 158652	Harderwijk
Netherlands	Isala /ID# 158653	Zwolle
Poland	Copernicus PL Sp. z o. o., WCO /ID# 160538	Gdansk
Poland	Szpitale Pomorskie Sp. z o.o /ID# 160536	Gdynia
Poland	Mrukmed. Lekarz Beata Madej Mruk i Partner /ID# 160537	Rzeszów	Podkarpackie
Portugal	IPO Lisboa FG, EPE /ID# 158995	Lisboa
Portugal	Centro Hospitalar Lisboa Norte, EPE /ID# 158687	Lisbon	Lisboa
Portugal	Hospital da Luz, SA /ID# 158996	Lisbon
Portugal	Unidade Local Saude Matosinhos /ID# 158682	Matosinhos
Portugal	Hospital CUF Porto /ID# 158685	Porto
Portugal	IPO Porto FG, EPE /ID# 158686	Porto
Romania	Spitalul Judetean de Urgenta A /ID# 160846	Alba
Romania	S.C. Centrul de Oncologie Sf. Nectarie S.R.L. /ID# 160847	Craiova	Dolj
Romania	Oncocenter Oncologie Clinica S /ID# 160848	Timisoara	Timis
Russian Federation	Arkhangelsk clinical oncology /ID# 159309	Arkhangelsk
Russian Federation	Kaluga Regional Clinical Oncol /ID# 160179	Kaluga
Russian Federation	National Medical Research Cntr /ID# 207436	Moscow	Moskovskaya Oblast
Russian Federation	Clinical Onco Dispensary /ID# 159307	Omsk
Russian Federation	PMI Euromedservice /ID# 159311	Pushkin
Russian Federation	LLC Novaya Klinika /ID# 205539	Pyatigorsk	Stavropol Skiy Kray
Russian Federation	Smolensk Regional Onc Clin Dis /ID# 159314	Smolensk
Russian Federation	LLC BioEq Ltd. /ID# 159310	St. Petersburg
Russian Federation	N.N. Petrov Research Inst Onc /ID# 159312	St. Petersburg
Serbia	Institut za onkologiju i radio /ID# 160058	Belgrade
Serbia	Klinicki centar Srbije /ID# 160024	Belgrade
Serbia	Clinical Center of Nis /ID# 160059	NIS	Nisavski Okrug
Serbia	Institute For Pulmonary Diseas /ID# 158813	Sremska Kamenica
Singapore	National Cancer Ctr Singapore /ID# 158803	Singapore
Singapore	National University Hospital /ID# 158802	Singapore
Spain	Hospital Clinic /ID# 159031	Barcelona
Spain	Hospital Santa Creu i Sant Pau /ID# 159028	Barcelona
Spain	Hospital General Universitario Gregorio Maranon /ID# 159025	Madrid
Spain	Hospital Universitario HM Sanchinarro /ID# 159024	Madrid
Spain	Hospital Clinico Universitario de Valencia /ID# 159027	Valencia
Sweden	Sahlgrenska US Gbg /ID# 159534	Göteborg	Vastra Gotalands Lan
Sweden	Uppsala University Hospital /ID# 159050	Uppsala
Taiwan	Taichung Veterans General Hosp /ID# 158866	Taichung City
Taiwan	National Cheng Kung University Hospital /ID# 158844	Tainan City	Tainan
Taiwan	National Taiwan University Hospital /ID# 158865	Taipei City	Taipei
Taiwan	Tri-Service General Hospital /ID# 158985	Taipei City	Taipei
Turkey	Hacettepe University Medical Faculty /ID# 159238	Altindag	Ankara
Turkey	Inonu Universitesi Turgut Ozal /ID# 159241	Battalgazi/malatya
Turkey	Dr. Suat Seren Gogus Has /ID# 159240	Izmir
Turkey	Ege University Medical Faculty /ID# 159239	Izmir
Turkey	Ataturk Gogus Hastaliklari ve /ID# 160056	Kecioren/ankara
Ukraine	Municipal institution /ID# 159867	Chernivtsi
Ukraine	Municipal institution Multifie /ID# 159121	Dnipro
Ukraine	Regional Center of Oncology /ID# 159123	Kharkiv
Ukraine	PE PMC Acinus, Medical and Diagnostic Center /ID# 159125	Kropyvnytskyi
Ukraine	ME Kryviy Rih Oncology Dispensary /ID# 159119	Kryviy RIH
Ukraine	Volyn Regional Medical Oncology Centre /ID# 159124	Lutsk
Ukraine	Communal Nonprofit Enterprise "Central City Clinical Hospital" of Uzhhorod City /ID# 159868	Uzhhorod
Ukraine	CI Zaporizhzhia Regional Clinical Oncological Dispensary /ID# 159122	Zaporizhzhia	Zaporizka Oblast
United Kingdom	United Lincolnshire Hospitals /ID# 159579	Boston
United Kingdom	Charing Cross Hospital /ID# 159582	London
United Kingdom	Guy's and St Thomas' NHS Found /ID# 159581	London	London, City Of
United Kingdom	Christie NHS Foundation Trust /ID# 159099	Manchester
United Kingdom	James Cook University Hospital /ID# 159583	Middlesborough
United Kingdom	Royal Preston Hospital /ID# 159578	Preston
United States	Georgia Cancer Center /ID# 160206	Atlanta	Georgia
United States	Univ Medical Ctr Brackenridge /ID# 156967	Austin	Texas
United States	Ochsner Clinic Foundation /ID# 160807	Baton Rouge	Louisiana
United States	Cedars-Sinai Medical Center /ID# 157102	Beverly Hills	California
United States	Dana-Farber Cancer Institute /ID# 160210	Boston	Massachusetts
United States	University of Vermont Medical Center /ID# 162317	Burlington	Vermont
United States	Gabrail Cancer Center Research /ID# 155920	Canton	Ohio
United States	UT Southwestern Medical Center /ID# 158150	Dallas	Texas
United States	NorthShore University HealthSystem - Evanston Hospital /ID# 157054	Evanston	Illinois
United States	Goshen Center for Cancer Care /ID# 155946	Goshen	Indiana
United States	Ingalls Memorial Hosp /ID# 155871	Harvey	Illinois
United States	Clearview Cancer Institute /ID# 155873	Huntsville	Alabama
United States	Cancer Specialists of North Florida - Southpoint /ID# 155828	Jacksonville	Florida
United States	Moore UC San Diego Cancer Center /ID# 156965	La Jolla	California
United States	Sparrow Regional Cancer Center, Sparrow Health System /ID# 157021	Lansing	Michigan
United States	Nebraska Hematology Oncology /ID# 155900	Lincoln	Nebraska
United States	Carti /Id# 156982	Little Rock	Arkansas
United States	Los Angeles Hematology Oncolog /ID# 155879	Los Angeles	California
United States	University of Louisville /ID# 155947	Louisville	Kentucky
United States	St. Luke's Mountain States Tumor Institute - Meridian /ID# 164550	Meridian	Idaho
United States	Mitchell Cancer Institute /ID# 158151	Mobile	Alabama
United States	West Virginia Univ School Med /ID# 155872	Morgantown	West Virginia
United States	Christiana Care Health Service /ID# 158171	Newark	Delaware
United States	UPMC Hillman Cancer Ctr /ID# 164403	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University /ID# 157055	Portland	Oregon
United States	University of California, Davis Comprehensive Cancer Center /ID# 157001	Sacramento	California
United States	St Jude Hospital dba St Joseph /ID# 155899	Santa Rosa	California
United States	University of Washington /ID# 162626	Seattle	Washington
United States	Medical Oncology Associates /ID# 156856	Spokane	Washington
United States	Highlands Oncology Group /ID# 155902	Springdale	Arkansas
United States	Icri /Id# 157090	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Australia,  Belarus,  Belgium,  Brazil,  Bulgaria,  Canada,  China,  Croatia,  Czechia,  Denmark,  France,  Germany,  Greece,  Hungary,  Italy,  Japan,  Korea, Republic of,  Latvia,  Mexico,  Netherlands,  Poland,  Portugal,  Romania,  Russian Federation,  Serbia,  Singapore,  Spain,  Sweden,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

References & Publications (1)

Morgensztern D, Besse B, Greillier L, Santana-Davila R, Ready N, Hann CL, Glisson BS, Farago AF, Dowlati A, Rudin CM, Le Moulec S, Lally S, Yalamanchili S, Wolf J, Govindan R, Carbone DP. Efficacy and Safety of Rovalpituzumab Tesirine in Third-Line and Beyond Patients with DLL3-Expressing, Relapsed/Refractory Small-Cell Lung Cancer: Results From the Phase II TRINITY Study. Clin Cancer Res. 2019 Dec 1;25(23):6958-6966. doi: 10.1158/1078-0432.CCR-19-1133. Epub 2019 Sep 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	OS is defined as the time from the date of randomization to the date of death from any cause. Participants were censored at the last date they were documented alive. After the End of treatment, survival information was collected at approximately 6-week intervals (or as requested by sponsor to support data analysis) continuing until the endpoint of death, the participant became lost to follow-up, AbbVie terminated the study, or until 12 February 2020. Calculated using the Kaplan-Meier product-limit method.	From randomization until the end of study; median time on follow-up was 20 and 20.6 months for the topotecan and rovalpituzumab tesirine arms, respectively.
Secondary	Progression Free Survival (PFS)	PFS is defined as the number of months from the date of randomization until the date of first progression or the date of a participant's death, whichever occurs first. If a participant neither experienced disease progression nor died, then the participant's data were censored at the last date of radiographic assessment that they were documented to be progression free. Calculated using the Kaplan-Meier product-limit method.; Radiographic tumor assessments for response were conducted by CT scanning according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Progressive Disease (PD) was defined as at least a 20% increase in the size of target lesions and an absolute increase of at least 5 mm taking as reference the smallest lesion size recorded since the treatment started (baseline or after), or the appearance of one or more new lesions.	From randomization until the end of study; median time on follow-up was 20 and 20.6 months for the topotecan and rovalpituzumab tesirine arms, respectively.
Secondary	Change From Baseline of the Physical Functioning Scale Score in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative Care (EORTC QLQ-C15-PAL) at Week 7	The EORTC QLQ-C15-PAL is an abbreviated 15-item version of the EORTC core quality of life questionnaire (EORTC QLQ-C30) developed for use in palliative care. The score of 'physical functioning scale' score ranges from 0 (very poor) to 100 (excellent).	Baseline, Week 7
Secondary	Objective Response Rate (ORR)	ORR is defined as the percentage of participants whose best overall response is either complete response (CR) or partial response (PR) according to RECIST version 1.1. Radiographic tumor assessments for response were conducted by CT scanning, and assessed from the date of randomization until disease progression or death, whichever came first. Any participant who did not meet CR or PR, including those who did not have post-baseline radiological assessments were considered non-responders.; CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Radiographic tumor assessments were conducted at baseline, every 6 weeks for 30 weeks, then every 9 weeks until progression or death; median time on follow-up was 20 and 20.6 months for the topotecan and rovalpituzumab tesirine arms, respectively.
Secondary	Clinical Benefit Rate (CBR)	CBR is defined as percentage of participants whose best overall response is CR, PR, or stable disease (SD) according to RECIST version 1.1. Radiographic tumor assessments for response were conducted by CT scanning, and assessed from the date of randomization until disease progression or death, whichever came first. Any participant who did not meet CR, PR, or SD, including those who did not have post-baseline radiological assessments were considered as experiencing no clinical benefit.; CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.	Radiographic tumor assessments were conducted at baseline, every 6 weeks for 30 weeks, then every 9 weeks until progression or death; median time on follow-up was 20 and 20.6 months for the topotecan and rovalpituzumab tesirine arms, respectively.
Secondary	Duration of Objective Response (DOR)	DOR is defined as the time between the date of first response (CR or PR, whichever is recorded first) to the date of the first documented tumor progression (per RECIST version 1.1) or death due to any cause, whichever comes first. Radiographic tumor assessments for response were conducted by CT scanning, and assessed from the date of randomization until disease progression or death, whichever came first. Any participant who did not meet CR or PR, including those who did not have post-baseline radiological assessments were considered non-responders.; CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Radiographic tumor assessments were conducted at baseline, every 6 weeks for 30 weeks, then every 9 weeks until progression or death; median time on follow-up was 20 and 20.6 months for the topotecan and rovalpituzumab tesirine arms, respectively.