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)

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03061812
• Collaborator: (none)
• Enrollment: 444
• Locations: 195
• Arms: 2
• Actual Duration (Months): 34.1
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Small Cell Lung Cancer	Drug: Rovalpituzumab tesirine; Drug: Topotecan; Drug: Dexamethasone	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 444 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: Apr 11, 2017
• Actual Primary Completion Date: Feb 12, 2020
• Actual Study Completion Date: Feb 12, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rovalpituzumab tesirine Rovalpituzumab tesirine IV administration (dosing based on actual body weight) on Day 1 of a 42-day cycle for 2 cycles, with up to 2 additional cycles permitted. Dexamethasone coadministered orally (PO) twice daily at a dose of 8 mg on Day -1, Day 1, and Day 2 of each 42-day cycle in which rovalpituzumab tesirine is administered.	Drug: Rovalpituzumab tesirine; Powder for solution for infusion in vials.; Other Names: Rova-T ; Drug: Dexamethasone; Oral tablet.
Active Comparator: Topotecan Topotecan given as an intravenous (IV) infusion over 30 minutes at a dose of 1.5 mg/m^2 on Days 1 to 5 of each 21-day cycle.	Drug: 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.

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) [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.]

   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.

Secondary Outcome Measures

1. Progression Free Survival (PFS) [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.]

   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.

2. 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 [Baseline, 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).

3. Objective Response Rate (ORR) [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.]

   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.

4. Clinical Benefit Rate (CBR) [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.]

   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.

5. Duration of Objective Response (DOR) [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.]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clearview Cancer Institute /ID# 155873	Huntsville	Alabama	United States	35805
2	Mitchell Cancer Institute /ID# 158151	Mobile	Alabama	United States	36604
3	Carti /Id# 156982	Little Rock	Arkansas	United States	72205
4	Highlands Oncology Group /ID# 155902	Springdale	Arkansas	United States	72762
5	Cedars-Sinai Medical Center /ID# 157102	Beverly Hills	California	United States	90211
6	Moore UC San Diego Cancer Center /ID# 156965	La Jolla	California	United States	92093
7	Los Angeles Hematology Oncolog /ID# 155879	Los Angeles	California	United States	90017
8	University of California, Davis Comprehensive Cancer Center /ID# 157001	Sacramento	California	United States	95817
9	St Jude Hospital dba St Joseph /ID# 155899	Santa Rosa	California	United States	95403
10	Icri /Id# 157090	Whittier	California	United States	90603
11	Christiana Care Health Service /ID# 158171	Newark	Delaware	United States	19713
12	Cancer Specialists of North Florida - Southpoint /ID# 155828	Jacksonville	Florida	United States	32256
13	Georgia Cancer Center /ID# 160206	Atlanta	Georgia	United States	30342
14	St. Luke's Mountain States Tumor Institute - Meridian /ID# 164550	Meridian	Idaho	United States	83712
15	NorthShore University HealthSystem - Evanston Hospital /ID# 157054	Evanston	Illinois	United States	60201
16	Ingalls Memorial Hosp /ID# 155871	Harvey	Illinois	United States	60426
17	Goshen Center for Cancer Care /ID# 155946	Goshen	Indiana	United States	46526
18	University of Louisville /ID# 155947	Louisville	Kentucky	United States	40202
19	Ochsner Clinic Foundation /ID# 160807	Baton Rouge	Louisiana	United States	70836-6455
20	Dana-Farber Cancer Institute /ID# 160210	Boston	Massachusetts	United States	02215
21	Sparrow Regional Cancer Center, Sparrow Health System /ID# 157021	Lansing	Michigan	United States	48912
22	Nebraska Hematology Oncology /ID# 155900	Lincoln	Nebraska	United States	68506
23	Gabrail Cancer Center Research /ID# 155920	Canton	Ohio	United States	44718
24	Oregon Health and Science University /ID# 157055	Portland	Oregon	United States	97239
25	UPMC Hillman Cancer Ctr /ID# 164403	Pittsburgh	Pennsylvania	United States	15232
26	Univ Medical Ctr Brackenridge /ID# 156967	Austin	Texas	United States	78701
27	UT Southwestern Medical Center /ID# 158150	Dallas	Texas	United States	75390-7208
28	University of Vermont Medical Center /ID# 162317	Burlington	Vermont	United States	05401-1473
29	University of Washington /ID# 162626	Seattle	Washington	United States	98109
30	Medical Oncology Associates /ID# 156856	Spokane	Washington	United States	99208
31	West Virginia Univ School Med /ID# 155872	Morgantown	West Virginia	United States	26506
32	Blacktown Hospital /ID# 158907	Blacktown	New South Wales	Australia	2148
33	St George Hospital /ID# 158855	Kogarah	New South Wales	Australia	2217
34	Southern Medical Day Care Ctr /ID# 158853	Wollongong	New South Wales	Australia	2500
35	The Prince Charles Hospital /ID# 158897	Chermside	Queensland	Australia	4032
36	Ballarat Health Service /ID# 158904	Ballarat	Victoria	Australia	3350
37	Austin Hospital /ID# 158898	Heidelberg	Victoria	Australia	3084
38	Bobruysk Interdistrict Onco. /ID# 169394	Bobruisk		Belarus	213825
39	State Institution Republican Scientific Practical Center of Oncology and Medica /ID# 159325	Lesnoy		Belarus	223040
40	Mogilev Reg. Oncologic dispe /ID# 159326	Mogilev		Belarus	212018
41	CHU Saint-Pierre /ID# 159521	Bruxelles	Bruxelles-Capitale	Belgium	1000
42	Grand Hôpital de Charleroi /ID# 158748	Charleroi	Hainaut	Belgium	6000
43	Cliniques universitaires Saint /ID# 158751	Brussels		Belgium	1200
44	Hopital de Jolimont /ID# 159755	Haine Saint Paul		Belgium	7100
45	UZ Leuven /ID# 158752	Leuven		Belgium	3000
46	CHU de Liege Sart Tilman /ID# 158753	Liege		Belgium	4000
47	CHU Charleroi (Vesale) /ID# 159756	Montigny-le-tilleul		Belgium	6110
48	Liga Norte Rio Grandense Cont. /ID# 159015	Natal	Rio Grande Do Norte	Brazil	59075-740
49	Associação Hospital Beneficente São Vicente de Paulo - Hospital São Vicente de P /ID# 159668	Passo Fundo	Rio Grande Do Sul	Brazil	99010-080
50	Fundacao Pio XII - Hospital de Cancer de Barretos /ID# 159017	Barretos	Sao Paulo	Brazil	14784-400
51	Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto /ID# 159666	Sao Jose Do Rio Preto	Sao Paulo	Brazil	15090-000
52	Instituto Nacional de Câncer José de Alencar Gomes da Silva (INCA) /ID# 159665	Rio de Janeiro		Brazil	20231-050
53	UMHAT Tsaritsa Joanna - ISUL /ID# 159641	Sofia		Bulgaria	1527
54	UMHAT Sv. Ivan Rilski /ID# 159642	Sofia		Bulgaria	1612
55	Cross Cancer Institute /ID# 159519	Edmonton	Alberta	Canada	T6G 1Z2
56	Juravinski Cancer Clinic /ID# 159514	Hamilton	Ontario	Canada	L8V 1C3
57	Hopital du Sacre Coeur Montreal /ID# 159515	Montreal	Quebec	Canada	H4J 1C5
58	CHU de Quebec-Universite Laval /ID# 159093	Quebec City	Quebec	Canada	G1R 2J6
59	Cisss Du Bas-Saint-Laurent Hopital Regional de Rimouski /Id# 208931	Rimouski	Quebec	Canada	G5L 5T1
60	Jilin Cancer Hosptial /ID# 204059	Changchun	Jilin	China	130000
61	Klinicki bolnicki centar Sestre milosrdnice /ID# 158811	Zagreb	Grad Zagreb	Croatia	10000
62	Klinika za plucne bolesti Jordanovac /ID# 159502	Zagreb	Grad Zagreb	Croatia	10000
63	Klinicki bolnicki centar Rijeka /ID# 159501	Rijeka	Primorsko-goranska Zupanija	Croatia	51000
64	Thomayerova nemocnice /ID# 159061	Prague	Praha 4	Czechia	140 59
65	Nemocnice Na Plesi s.r.o. /ID# 161190	Nová Ves pod Pleší	Pribram	Czechia	262 04
66	Nemocnice Rudolfa a Stefanie /ID# 159652	Benesov		Czechia	256 01
67	Nemocnice Horovice a.s. /ID# 161191	Horovice		Czechia	268 31
68	Krajska nemocnice Liberec a.s. /ID# 159653	Liberec		Czechia	602 00
69	Herlev Hospital /ID# 158049	Herlev	Hovedstaden	Denmark	2730
70	Odense Universitets Hospital /ID# 158050	Odense C	Syddanmark	Denmark	5000
71	Rigshospitalet, Finsen Centre /ID# 158051	Copenhagen		Denmark	2100
72	Hopital Haut-Lévêque /ID# 160558	Pessac CEDEX	Gironde	France	33604
73	Assis.Publique-Hopital Nord /ID# 160554	Marseille	Provence-Alpes-Cote-d Azur	France	13105
74	Centre Leon Berard /ID# 160561	Lyon CEDEX 08	Rhone	France	69373
75	Centre Hosp Intercommunal de Creteil /ID# 162684	Creteil	Val-de-Marne	France	94000
76	Assistance Publique- Hopitaux /ID# 160552	Paris		France	75020
77	Hospital Pontchaillou /ID# 160555	Rennes		France	35033
78	KH Martha-Maria Halle Dolau /ID# 158796	Halle (Saale)	Sachsen-Anhalt	Germany	06120
79	Evangelische Lungenklinik Berl /ID# 159168	Berlin		Germany	13125
80	Asklepios Fachkliniken M. Gaut /ID# 158791	Gauting		Germany	82131
81	Lungen Clinic Grosshansdorf /ID# 158770	Grosshansdorf		Germany	22927
82	Thoraxklinik Heidelberg gGmbH /ID# 159169	Heidelberg		Germany	69126
83	Klinikum Kassel /ID# 158788	Kassel		Germany	34125
84	Klinik Loewenstein GmbH /ID# 159167	Löwenstein		Germany	74245
85	General Hospital of Chest Diseases of Athens SOTIRIA /ID# 159165	Athens		Greece	11527
86	Metropolitan Hospital /ID# 159162	Athens		Greece	18547
87	University Hospital of Ioannin /ID# 159163	Ioannina		Greece	45500
88	Euromedica General Clinic /ID# 159161	Thessaloniki		Greece	54645
89	Torokbalinti Tudogyogyintezet /ID# 207053	Budapest	Pest	Hungary	2045
90	Semmelweis Egyetem /ID# 161197	Budapest		Hungary	1085
91	Orszagos Koranyi Pulmonologiai Intezet /ID# 158967	Budapest		Hungary	1122
92	Dup_Debreceni Egyetem Klinikai Központ /ID# 161209	Debrecen		Hungary	4032
93	Veszprem Megyei Tuedoegyogyint /ID# 162607	Farkasgyepu		Hungary	8582
94	Petz Aladar Megyei Oktato Korh /ID# 158978	Gyor		Hungary	9023
95	Matrai Gyogyintezet /ID# 158979	Matrahaza		Hungary	3233
96	AUSL 8 Arezzo Ospedale San Don /ID# 160967	Arezzo		Italy	52100
97	Istituto Europeo di Oncologia /ID# 158942	Milan		Italy	20141
98	A.O.U. San Luigi Gonzaga /ID# 158945	Orbassano		Italy	10043
99	Ospedale Santa Maria delle Cro /ID# 158940	Ravenna		Italy	48121
100	IFO Istituto Nazionale Tumori /ID# 158941	Rome		Italy	00144
101	Aichi Cancer Center Hospital /ID# 164975	Nagoya-shi	Aichi	Japan	464-8681
102	National Cancer Center Hospital East /ID# 165726	Kashiwa-shi	Chiba	Japan	277-8577
103	Kyushu University Hospital /ID# 165723	Fukuoka-shi	Fukuoka	Japan	812-8582
104	Kurume University Hospital /ID# 164586	Kurume-shi	Fukuoka	Japan	830-0011
105	Hokkaido Cancer Center /ID# 165237	Sapporo-shi	Hokkaido	Japan	003-0804
106	Hyogo Cancer Center /ID# 165125	Akashi-shi	Hyogo	Japan	673-8558
107	Himeji Medical Center /ID# 165893	Himeji-shi	Hyogo	Japan	670-0012
108	Duplicate_Kanazawa University Hospital /ID# 165129	Kanazawa-shi	Ishikawa	Japan	920-8641
109	Yokohama City University Hospital /ID# 165748	Yokohama-shi	Kanagawa	Japan	236-0004
110	Kanagawa Cardiovascular and Respiratory Center /ID# 164374	Yokohama-shi	Kanagawa	Japan	236-0051
111	Sendai Kousei Hospital /ID# 166061	Sendai-shi	Miyagi	Japan	980-0873
112	Japanese Red Cross Okayama Hospital /ID# 165156	Okayama-shi	Okayama	Japan	700-8607
113	Kansai Medical University Hospital /ID# 165055	Hirakata-shi	Osaka	Japan	573-1191
114	Kindai University Hospital /ID# 166394	Osaka-sayama-shi	Osaka	Japan	589-8511
115	Osaka City General Hospital /ID# 165717	Osaka-shi	Osaka	Japan	534-0021
116	Shizuoka Cancer Center /ID# 166466	Sunto-gun	Shizuoka	Japan	411-8777
117	Tokushima University Hospital /ID# 165812	Tokushima-shi	Tokushima	Japan	770-8503
118	National Cancer Center Hospital /ID# 166768	Chuo-ku	Tokyo	Japan	104-0045
119	The Cancer Institute Hospital Of JFCR /ID# 166249	Koto-ku	Tokyo	Japan	135-8550
120	Duplicate_Showa University Hospital /ID# 165574	Shinagawa-ku	Tokyo	Japan	142-0054
121	Wakayama Medical University /ID# 166032	Wakayama-shi	Wakayama	Japan	641-8510
122	Matsusaka City Hospital /ID# 166126	Matsusaka-shi MIE		Japan	515-8544
123	Kanagawa Cancer Center /ID# 165816	Yokohama		Japan	241-0815
124	Dong-A University Hospital /ID# 159296	Busan	Busan Gwang Yeogsi	Korea, Republic of	49201
125	CHA Bundang Medical center CHA University /ID# 204416	Seongnam si	Gyeonggido	Korea, Republic of	13496
126	Chonnam National University Hospital /ID# 159294	Gwangju	Jeonranamdo	Korea, Republic of	61469
127	Kyungpook National University Chilgok Hospital /ID# 159292	Daegu	Seoul Teugbyeolsi	Korea, Republic of	41404
128	Yonsei University Health System, Severance Hospital /ID# 159288	Seodaemun-gu	Seoul Teugbyeolsi	Korea, Republic of	03722
129	Korea University Guro Hospital /ID# 159293	Seoul	Seoul Teugbyeolsi	Korea, Republic of	08308
130	Chungbuk National University /ID# 159291	Cheongju-si		Korea, Republic of	28644
131	Asan Medical Center /ID# 159290	Seoul		Korea, Republic of	05505
132	Pauls Stradins Clinical /ID# 158713	Riga		Latvia	LV-1002
133	Riga East Clinical University /ID# 158714	Riga		Latvia	LV-1079
134	Centro de Investigación Clinica Chapultepec /ID# 161000	Morelia	Michoacan	Mexico	58260
135	Health Pharma Professional Research S.A de C.V /ID# 160020	Del. Benito Juárez		Mexico	03810
136	Universitair Medisch Centrum Groningen /ID# 158088	Groningen		Netherlands	9713 GZ
137	Ziekenhuis St. Jansdal /ID# 158652	Harderwijk		Netherlands	3844 DG
138	Isala /ID# 158653	Zwolle		Netherlands	8025 AB
139	Mrukmed. Lekarz Beata Madej Mruk i Partner /ID# 160537	Rzeszów	Podkarpackie	Poland	35-021
140	Copernicus PL Sp. z o. o., WCO /ID# 160538	Gdansk		Poland	80-219
141	Szpitale Pomorskie Sp. z o.o /ID# 160536	Gdynia		Poland	81-519
142	Centro Hospitalar Lisboa Norte, EPE /ID# 158687	Lisbon	Lisboa	Portugal	1769-001
143	IPO Lisboa FG, EPE /ID# 158995	Lisboa		Portugal	1099-023
144	Hospital da Luz, SA /ID# 158996	Lisbon		Portugal	1500-650
145	Unidade Local Saude Matosinhos /ID# 158682	Matosinhos		Portugal	4464-513
146	Hospital CUF Porto /ID# 158685	Porto		Portugal	4100-180
147	IPO Porto FG, EPE /ID# 158686	Porto		Portugal	4200-072
148	S.C. Centrul de Oncologie Sf. Nectarie S.R.L. /ID# 160847	Craiova	Dolj	Romania	200347
149	Oncocenter Oncologie Clinica S /ID# 160848	Timisoara	Timis	Romania	300166
150	Spitalul Judetean de Urgenta A /ID# 160846	Alba		Romania	510077
151	National Medical Research Cntr /ID# 207436	Moscow	Moskovskaya Oblast	Russian Federation	115478
152	LLC Novaya Klinika /ID# 205539	Pyatigorsk	Stavropol Skiy Kray	Russian Federation	357500
153	Arkhangelsk clinical oncology /ID# 159309	Arkhangelsk		Russian Federation	163045
154	Kaluga Regional Clinical Oncol /ID# 160179	Kaluga		Russian Federation	284007
155	Clinical Onco Dispensary /ID# 159307	Omsk		Russian Federation	644013
156	PMI Euromedservice /ID# 159311	Pushkin		Russian Federation	196603
157	Smolensk Regional Onc Clin Dis /ID# 159314	Smolensk		Russian Federation	214009
158	LLC BioEq Ltd. /ID# 159310	St. Petersburg		Russian Federation	197342
159	N.N. Petrov Research Inst Onc /ID# 159312	St. Petersburg		Russian Federation	197758
160	Clinical Center of Nis /ID# 160059	NIS	Nisavski Okrug	Serbia	18000
161	Institut za onkologiju i radio /ID# 160058	Belgrade		Serbia	11000
162	Klinicki centar Srbije /ID# 160024	Belgrade		Serbia	11000
163	Institute For Pulmonary Diseas /ID# 158813	Sremska Kamenica		Serbia	21204
164	National University Hospital /ID# 158802	Singapore		Singapore	119074
165	National Cancer Ctr Singapore /ID# 158803	Singapore		Singapore	169610
166	Hospital Clinic /ID# 159031	Barcelona		Spain	08036
167	Hospital Santa Creu i Sant Pau /ID# 159028	Barcelona		Spain	08041
168	Hospital General Universitario Gregorio Maranon /ID# 159025	Madrid		Spain	28007
169	Hospital Universitario HM Sanchinarro /ID# 159024	Madrid		Spain	28050
170	Hospital Clinico Universitario de Valencia /ID# 159027	Valencia		Spain	46010
171	Sahlgrenska US Gbg /ID# 159534	Göteborg	Vastra Gotalands Lan	Sweden	413 46
172	Uppsala University Hospital /ID# 159050	Uppsala		Sweden	75185
173	National Cheng Kung University Hospital /ID# 158844	Tainan City	Tainan	Taiwan	70403
174	National Taiwan University Hospital /ID# 158865	Taipei City	Taipei	Taiwan	100
175	Tri-Service General Hospital /ID# 158985	Taipei City	Taipei	Taiwan	11490
176	Taichung Veterans General Hosp /ID# 158866	Taichung City		Taiwan	40705
177	Hacettepe University Medical Faculty /ID# 159238	Altindağ	Ankara	Turkey	06250
178	Inonu Universitesi Turgut Ozal /ID# 159241	Battalgazi/malatya		Turkey	44280
179	Ege University Medical Faculty /ID# 159239	Izmir		Turkey	35040
180	Dr. Suat Seren Gogus Has /ID# 159240	Izmir		Turkey	35110
181	Ataturk Gogus Hastaliklari ve /ID# 160056	Kecioren/ankara		Turkey	06280
182	CI Zaporizhzhia Regional Clinical Oncological Dispensary /ID# 159122	Zaporizhzhia	Zaporizka Oblast	Ukraine	69040
183	Municipal institution /ID# 159867	Chernivtsi		Ukraine	58013
184	Municipal institution Multifie /ID# 159121	Dnipro		Ukraine	49102
185	Regional Center of Oncology /ID# 159123	Kharkiv		Ukraine	61070
186	PE PMC Acinus, Medical and Diagnostic Center /ID# 159125	Kropyvnytskyi		Ukraine	25006
187	ME Kryviy Rih Oncology Dispensary /ID# 159119	Kryviy RIH		Ukraine	50048
188	Volyn Regional Medical Oncology Centre /ID# 159124	Lutsk		Ukraine	43018
189	Communal Nonprofit Enterprise "Central City Clinical Hospital" of Uzhhorod City /ID# 159868	Uzhhorod		Ukraine	88000
190	Guy's and St Thomas' NHS Found /ID# 159581	London	London, City Of	United Kingdom	SE1 9RT
191	United Lincolnshire Hospitals /ID# 159579	Boston		United Kingdom	PE21 9QS
192	Charing Cross Hospital /ID# 159582	London		United Kingdom	W6 8RF
193	Christie NHS Foundation Trust /ID# 159099	Manchester		United Kingdom	M20 4BX
194	James Cook University Hospital /ID# 159583	Middlesborough		United Kingdom	TS4 3BW
195	Royal Preston Hospital /ID# 159578	Preston		United Kingdom	PR2 9HT

Sponsors and Collaborators

• AbbVie

Investigators

• Study Director: AbbVie Inc., AbbVie

Study Documents (Full-Text)

• Study Protocol - Jan 8, 2019
• Statistical Analysis Plan - Mar 13, 2020

More Information

Publications

• 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.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT03061812
• Other Study ID Numbers: M16-289; 2016-003726-17
• First Posted: Feb 23, 2017
• Last Update Posted: Feb 23, 2021
• Last Verified: Feb 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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
• Keywords provided by AbbVie: Small cell lung cancer (SCLC); Delta-like protein 3 (DLL3); rovalpituzumab tesirine; topotecan; metastatic
• Additional relevant MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma; Disease Progression; Dexamethasone; Topotecan

Study Results

Participant Flow

Arm/Group Title	Topotecan	Rovalpituzumab Tesirine
Arm/Group Description	Topotecan given as an intravenous (IV) infusion over 30 minutes at a dose of 1.5 mg/m^2 on Days 1 to 5 of each 21-day cycle.	Rovalpituzumab tesirine IV administration (dosing based on actual body weight) on Day 1 of a 42-day cycle for 2 cycles, with up to 2 additional cycles permitted. Dexamethasone coadministered orally (PO) twice daily at a dose of 8 mg on Day -1, Day 1, and Day 2 of each 42-day cycle in which rovalpituzumab tesirine is administered.
Period Title: Overall Study
STARTED	148	296
COMPLETED	148	296
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Topotecan	Rovalpituzumab Tesirine	Total
Arm/Group Description	Topotecan given as an intravenous (IV) infusion over 30 minutes at a dose of 1.5 mg/m^2 on Days 1 to 5 of each 21-day cycle.	Rovalpituzumab tesirine IV administration (dosing based on actual body weight) on Day 1 of a 42-day cycle for 2 cycles, with up to 2 additional cycles permitted. Dexamethasone coadministered orally (PO) twice daily at a dose of 8 mg on Day -1, Day 1, and Day 2 of each 42-day cycle in which rovalpituzumab tesirine is administered.	Total of all reporting groups
Overall Participants	148	296	444
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.4 (8.72)	63.0 (8.57)	63.1 (8.61)
Sex: Female, Male (Count of Participants)
Female	62 41.9%	105 35.5%	167 37.6%
Male	86 58.1%	191 64.5%	277 62.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 1.4%	9 3%	11 2.5%
Not Hispanic or Latino	146 98.6%	287 97%	433 97.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.7%	0 0%	1 0.2%
Asian	23 15.5%	57 19.3%	80 18%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.3%	1 0.2%
Black or African American	2 1.4%	0 0%	2 0.5%
White	122 82.4%	236 79.7%	358 80.6%
More than one race	0 0%	2 0.7%	2 0.5%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Randomized participants

Arm/Group Title	Topotecan	Rovalpituzumab Tesirine
Arm/Group Description	Topotecan given as an intravenous (IV) infusion over 30 minutes at a dose of 1.5 mg/m^2 on Days 1 to 5 of each 21-day cycle.	Rovalpituzumab tesirine IV administration (dosing based on actual body weight) on Day 1 of a 42-day cycle for 2 cycles, with up to 2 additional cycles permitted. Dexamethasone coadministered orally (PO) twice daily at a dose of 8 mg on Day -1, Day 1, and Day 2 of each 42-day cycle in which rovalpituzumab tesirine is administered.
Measure Participants	148	296
Median (95% Confidence Interval) [months]	8.57	6.34

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Topotecan, Rovalpituzumab Tesirine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0051
	Comments
	Method	Log Rank
	Comments	Two-sided p-value stratified by the randomization stratification factors.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.46
	Confidence Interval	(2-Sided) 95%; 1.17 to 1.82
	Parameter Dispersion	Type: Value:
	Estimation Comments	Calculated using a Cox proportional hazards regression model, with treatment and randomization stratification factors as covariates.

2. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Randomized participants

Arm/Group Title	Topotecan	Rovalpituzumab Tesirine
Arm/Group Description	Topotecan given as an intravenous (IV) infusion over 30 minutes at a dose of 1.5 mg/m^2 on Days 1 to 5 of each 21-day cycle.	Rovalpituzumab tesirine IV administration (dosing based on actual body weight) on Day 1 of a 42-day cycle for 2 cycles, with up to 2 additional cycles permitted. Dexamethasone coadministered orally (PO) twice daily at a dose of 8 mg on Day -1, Day 1, and Day 2 of each 42-day cycle in which rovalpituzumab tesirine is administered.
Measure Participants	148	296
Median (95% Confidence Interval) [months]	4.27	3.02

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Topotecan, Rovalpituzumab Tesirine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Log Rank
	Comments	Two-sided p-value stratified by the randomization stratification factors.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.51
	Confidence Interval	(2-Sided) 95%; 1.22 to 1.87
	Parameter Dispersion	Type: Value:
	Estimation Comments	Calculated using a Cox proportional hazards regression model, with treatment and randomization stratification factors as covariates.

3. Secondary Outcome

Title	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
Description	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).
Time Frame	Baseline, Week 7

Outcome Measure Data

Analysis Population Description

Randomized participants with an assessment at baseline and Week 7.

Arm/Group Title	Topotecan	Rovalpituzumab Tesirine
Arm/Group Description	Topotecan given as an intravenous (IV) infusion over 30 minutes at a dose of 1.5 mg/m^2 on Days 1 to 5 of each 21-day cycle.	Rovalpituzumab tesirine IV administration (dosing based on actual body weight) on Day 1 of a 42-day cycle for 2 cycles, with up to 2 additional cycles permitted. Dexamethasone coadministered orally (PO) twice daily at a dose of 8 mg on Day -1, Day 1, and Day 2 of each 42-day cycle in which rovalpituzumab tesirine is administered.
Measure Participants	93	217
Least Squares Mean (95% Confidence Interval) [score on a scale]	-7.16	-7.66

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Topotecan, Rovalpituzumab Tesirine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS Mean of Difference
	Estimated Value	-0.50
	Confidence Interval	(2-Sided) 95%; -5.66 to 4.65
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.62
	Estimation Comments

4. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Randomized participants with measurable disease at baseline.

Arm/Group Title	Topotecan	Rovalpituzumab Tesirine
Arm/Group Description	Topotecan given as an intravenous (IV) infusion over 30 minutes at a dose of 1.5 mg/m^2 on Days 1 to 5 of each 21-day cycle.	Rovalpituzumab tesirine IV administration (dosing based on actual body weight) on Day 1 of a 42-day cycle for 2 cycles, with up to 2 additional cycles permitted. Dexamethasone coadministered orally (PO) twice daily at a dose of 8 mg on Day -1, Day 1, and Day 2 of each 42-day cycle in which rovalpituzumab tesirine is administered.
Measure Participants	129	287
Number (95% Confidence Interval) [percentage of participants]	20.9 14.1%	14.6 4.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Topotecan, Rovalpituzumab Tesirine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3352
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by the randomization stratification factors.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.68
	Confidence Interval	(2-Sided) 95%; 0.39 to 1.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Clinical Benefit Rate (CBR)
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Randomized participants with measurable disease at baseline.

Arm/Group Title	Topotecan	Rovalpituzumab Tesirine
Arm/Group Description	Topotecan given as an intravenous (IV) infusion over 30 minutes at a dose of 1.5 mg/m^2 on Days 1 to 5 of each 21-day cycle.	Rovalpituzumab tesirine IV administration (dosing based on actual body weight) on Day 1 of a 42-day cycle for 2 cycles, with up to 2 additional cycles permitted. Dexamethasone coadministered orally (PO) twice daily at a dose of 8 mg on Day -1, Day 1, and Day 2 of each 42-day cycle in which rovalpituzumab tesirine is administered.
Measure Participants	129	287
Number (95% Confidence Interval) [percentage of participants]	43.4 29.3%	35.9 12.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Topotecan, Rovalpituzumab Tesirine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0358
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by the randomization stratification factors.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95%; 0.47 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Duration of Objective Response (DOR)
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Randomized participants with measurable disease at baseline, and a response.

Arm/Group Title	Topotecan	Rovalpituzumab Tesirine
Arm/Group Description	Topotecan given as an intravenous (IV) infusion over 30 minutes at a dose of 1.5 mg/m^2 on Days 1 to 5 of each 21-day cycle.	Rovalpituzumab tesirine IV administration (dosing based on actual body weight) on Day 1 of a 42-day cycle for 2 cycles, with up to 2 additional cycles permitted. Dexamethasone coadministered orally (PO) twice daily at a dose of 8 mg on Day -1, Day 1, and Day 2 of each 42-day cycle in which rovalpituzumab tesirine is administered.
Measure Participants	27	42
Median (95% Confidence Interval) [months]	4.86	3.52

Adverse Events

Time Frame	All-cause mortality is reported from enrollment to the end of study; median time on follow-up was 20 and 20.6 months for the topotecan and rovalpituzumab tesirine arms, respectively. Treatment-emergent adverse events and serious adverse events were collected from first dose of study drug until 70 days after the last dose of study drug; mean duration on study drug was 14.8 weeks and 11.3 weeks for the topotecan and rovalpituzumab tesirine arms, respectively.
Adverse Event Reporting Description	All-cause mortality: all randomized participants. Adverse events: all participants who received at least 1 dose of study drug.
Arm/Group Title	Topotecan		Rovalpituzumab Tesirine
Arm/Group Description	Topotecan given as an intravenous (IV) infusion over 30 minutes at a dose of 1.5 mg/m^2 on Days 1 to 5 of each 21-day cycle.		Rovalpituzumab tesirine IV administration (dosing based on actual body weight) on Day 1 of a 42-day cycle for 2 cycles, with up to 2 additional cycles permitted. Dexamethasone coadministered orally (PO) twice daily at a dose of 8 mg on Day -1, Day 1, and Day 2 of each 42-day cycle in which rovalpituzumab tesirine is administered.
All Cause Mortality
	Topotecan		Rovalpituzumab Tesirine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	115/148 (77.7%)		262/296 (88.5%)
Serious Adverse Events
	Topotecan		Rovalpituzumab Tesirine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	74/129 (57.4%)		160/287 (55.7%)
Blood and lymphatic system disorders
ANAEMIA	4/129 (3.1%)	4	4/287 (1.4%)	4
FEBRILE NEUTROPENIA	11/129 (8.5%)	13	4/287 (1.4%)	4
HAEMATOTOXICITY	1/129 (0.8%)	1	0/287 (0%)	0
LEUKOPENIA	1/129 (0.8%)	1	0/287 (0%)	0
NEUTROPENIA	6/129 (4.7%)	6	0/287 (0%)	0
PANCYTOPENIA	2/129 (1.6%)	2	0/287 (0%)	0
THROMBOCYTOPENIA	10/129 (7.8%)	10	5/287 (1.7%)	5
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION	1/129 (0.8%)	1	0/287 (0%)	0
ANGINA UNSTABLE	1/129 (0.8%)	1	0/287 (0%)	0
ARRHYTHMIA	0/129 (0%)	0	1/287 (0.3%)	1
ATRIAL FIBRILLATION	0/129 (0%)	0	1/287 (0.3%)	1
CARDIAC ARREST	0/129 (0%)	0	2/287 (0.7%)	2
CARDIAC FAILURE	0/129 (0%)	0	3/287 (1%)	4
CARDIAC FAILURE CONGESTIVE	0/129 (0%)	0	1/287 (0.3%)	2
CARDIAC TAMPONADE	0/129 (0%)	0	1/287 (0.3%)	1
PERICARDIAL EFFUSION	0/129 (0%)	0	1/287 (0.3%)	1
Congenital, familial and genetic disorders
APLASIA	1/129 (0.8%)	1	0/287 (0%)	0
Ear and labyrinth disorders
VERTIGO	1/129 (0.8%)	1	0/287 (0%)	0
Endocrine disorders
ADRENAL INSUFFICIENCY	0/129 (0%)	0	1/287 (0.3%)	1
INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION	1/129 (0.8%)	1	1/287 (0.3%)	1
Gastrointestinal disorders
ABDOMINAL PAIN	1/129 (0.8%)	1	2/287 (0.7%)	3
ABDOMINAL PAIN LOWER	0/129 (0%)	0	1/287 (0.3%)	1
ABDOMINAL PAIN UPPER	0/129 (0%)	0	1/287 (0.3%)	1
ASCITES	0/129 (0%)	0	1/287 (0.3%)	1
COLITIS	0/129 (0%)	0	1/287 (0.3%)	1
CONSTIPATION	0/129 (0%)	0	4/287 (1.4%)	4
DIARRHOEA	0/129 (0%)	0	2/287 (0.7%)	2
DYSPHAGIA	0/129 (0%)	0	3/287 (1%)	3
GASTRIC HAEMORRHAGE	0/129 (0%)	0	1/287 (0.3%)	1
GASTRITIS	0/129 (0%)	0	1/287 (0.3%)	1
GASTROINTESTINAL HAEMORRHAGE	1/129 (0.8%)	1	1/287 (0.3%)	1
LARGE INTESTINE PERFORATION	0/129 (0%)	0	1/287 (0.3%)	1
NAUSEA	0/129 (0%)	0	2/287 (0.7%)	2
PANCREATITIS	0/129 (0%)	0	3/287 (1%)	4
PANCREATITIS ACUTE	0/129 (0%)	0	1/287 (0.3%)	1
STOMATITIS	0/129 (0%)	0	1/287 (0.3%)	1
SUBILEUS	0/129 (0%)	0	1/287 (0.3%)	1
VOMITING	1/129 (0.8%)	1	1/287 (0.3%)	1
General disorders
ASTHENIA	0/129 (0%)	0	2/287 (0.7%)	3
CHEST PAIN	2/129 (1.6%)	2	0/287 (0%)	0
DEATH	0/129 (0%)	0	2/287 (0.7%)	2
DISEASE PROGRESSION	1/129 (0.8%)	1	0/287 (0%)	0
FACE OEDEMA	0/129 (0%)	0	1/287 (0.3%)	1
FATIGUE	0/129 (0%)	0	6/287 (2.1%)	6
GENERAL PHYSICAL HEALTH DETERIORATION	6/129 (4.7%)	7	8/287 (2.8%)	10
MALAISE	0/129 (0%)	0	1/287 (0.3%)	1
MULTIPLE ORGAN DYSFUNCTION SYNDROME	0/129 (0%)	0	1/287 (0.3%)	1
NON-CARDIAC CHEST PAIN	1/129 (0.8%)	1	1/287 (0.3%)	1
OEDEMA PERIPHERAL	0/129 (0%)	0	1/287 (0.3%)	1
POLYSEROSITIS	0/129 (0%)	0	1/287 (0.3%)	1
PYREXIA	3/129 (2.3%)	3	0/287 (0%)	0
SEROSITIS	0/129 (0%)	0	1/287 (0.3%)	1
Hepatobiliary disorders
CHOLANGITIS	1/129 (0.8%)	1	0/287 (0%)	0
CHOLECYSTITIS	0/129 (0%)	0	1/287 (0.3%)	1
CHOLECYSTITIS ACUTE	0/129 (0%)	0	2/287 (0.7%)	2
CHOLESTASIS	0/129 (0%)	0	1/287 (0.3%)	2
DRUG-INDUCED LIVER INJURY	0/129 (0%)	0	1/287 (0.3%)	1
HEPATIC FAILURE	1/129 (0.8%)	1	1/287 (0.3%)	1
JAUNDICE CHOLESTATIC	0/129 (0%)	0	1/287 (0.3%)	1
Immune system disorders
ANAPHYLACTIC REACTION	0/129 (0%)	0	1/287 (0.3%)	1
Infections and infestations
ABSCESS	0/129 (0%)	0	1/287 (0.3%)	1
ATYPICAL PNEUMONIA	0/129 (0%)	0	1/287 (0.3%)	1
BRONCHITIS	1/129 (0.8%)	1	1/287 (0.3%)	1
CANDIDA INFECTION	1/129 (0.8%)	1	0/287 (0%)	0
GASTROENTERITIS	1/129 (0.8%)	1	0/287 (0%)	0
GASTROENTERITIS VIRAL	0/129 (0%)	0	1/287 (0.3%)	1
HERPES ZOSTER	0/129 (0%)	0	2/287 (0.7%)	2
INFECTIVE EXACERBATION OF CHRONIC OBSTRUCTIVE AIRWAYS DISEASE	0/129 (0%)	0	1/287 (0.3%)	1
INFLUENZA	2/129 (1.6%)	2	0/287 (0%)	0
LOWER RESPIRATORY TRACT INFECTION	0/129 (0%)	0	5/287 (1.7%)	6
LUNG ABSCESS	1/129 (0.8%)	1	1/287 (0.3%)	1
NEUTROPENIC SEPSIS	1/129 (0.8%)	1	0/287 (0%)	0
ORCHITIS	1/129 (0.8%)	1	0/287 (0%)	0
PERITONITIS	0/129 (0%)	0	1/287 (0.3%)	1
PNEUMONIA	6/129 (4.7%)	6	19/287 (6.6%)	26
PNEUMONIA NECROTISING	0/129 (0%)	0	1/287 (0.3%)	1
PNEUMONIA STAPHYLOCOCCAL	0/129 (0%)	0	1/287 (0.3%)	1
RESPIRATORY SYNCYTIAL VIRUS INFECTION	0/129 (0%)	0	1/287 (0.3%)	1
RESPIRATORY TRACT INFECTION	0/129 (0%)	0	3/287 (1%)	3
RESPIRATORY TRACT INFECTION VIRAL	0/129 (0%)	0	1/287 (0.3%)	1
SALMONELLOSIS	0/129 (0%)	0	1/287 (0.3%)	1
SEPSIS	2/129 (1.6%)	2	0/287 (0%)	0
SEPTIC SHOCK	0/129 (0%)	0	2/287 (0.7%)	2
STAPHYLOCOCCAL INFECTION	1/129 (0.8%)	1	0/287 (0%)	0
Injury, poisoning and procedural complications
CONTUSION	0/129 (0%)	0	1/287 (0.3%)	1
EYELID CONTUSION	0/129 (0%)	0	1/287 (0.3%)	1
FALL	1/129 (0.8%)	1	1/287 (0.3%)	1
HEAT STROKE	0/129 (0%)	0	1/287 (0.3%)	1
SPINAL COMPRESSION FRACTURE	0/129 (0%)	0	1/287 (0.3%)	1
THERMAL BURN	0/129 (0%)	0	1/287 (0.3%)	1
Investigations
BLOOD CREATININE INCREASED	0/129 (0%)	0	1/287 (0.3%)	1
CULTURE URINE POSITIVE	0/129 (0%)	0	1/287 (0.3%)	1
GAMMA-GLUTAMYLTRANSFERASE INCREASED	0/129 (0%)	0	1/287 (0.3%)	1
GENERAL PHYSICAL CONDITION ABNORMAL	1/129 (0.8%)	1	1/287 (0.3%)	1
LIPASE INCREASED	0/129 (0%)	0	1/287 (0.3%)	1
NEUTROPHIL COUNT DECREASED	1/129 (0.8%)	1	0/287 (0%)	0
PLATELET COUNT DECREASED	1/129 (0.8%)	1	0/287 (0%)	0
Metabolism and nutrition disorders
CACHEXIA	0/129 (0%)	0	1/287 (0.3%)	1
DECREASED APPETITE	1/129 (0.8%)	1	2/287 (0.7%)	2
DIABETES MELLITUS INADEQUATE CONTROL	0/129 (0%)	0	1/287 (0.3%)	1
HYPERGLYCAEMIA	1/129 (0.8%)	1	2/287 (0.7%)	2
HYPOGLYCAEMIA	0/129 (0%)	0	1/287 (0.3%)	1
HYPOKALAEMIA	1/129 (0.8%)	1	0/287 (0%)	0
HYPONATRAEMIA	3/129 (2.3%)	6	3/287 (1%)	3
Musculoskeletal and connective tissue disorders
BACK PAIN	1/129 (0.8%)	1	1/287 (0.3%)	1
BONE PAIN	1/129 (0.8%)	1	0/287 (0%)	0
MUSCULAR WEAKNESS	1/129 (0.8%)	1	1/287 (0.3%)	1
OSTEOPOROSIS	0/129 (0%)	0	1/287 (0.3%)	2
PAIN IN EXTREMITY	0/129 (0%)	0	1/287 (0.3%)	1
PATHOLOGICAL FRACTURE	0/129 (0%)	0	1/287 (0.3%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
CANCER PAIN	1/129 (0.8%)	1	0/287 (0%)	0
GASTROINTESTINAL NEOPLASM	0/129 (0%)	0	1/287 (0.3%)	1
INFECTED NEOPLASM	0/129 (0%)	0	1/287 (0.3%)	1
LUNG NEOPLASM	1/129 (0.8%)	1	0/287 (0%)	0
LUNG NEOPLASM MALIGNANT	1/129 (0.8%)	1	0/287 (0%)	0
MALIGNANT NEOPLASM OF SPINAL CORD	1/129 (0.8%)	1	0/287 (0%)	0
MALIGNANT NEOPLASM PROGRESSION	17/129 (13.2%)	19	30/287 (10.5%)	32
METASTASES TO MENINGES	0/129 (0%)	0	1/287 (0.3%)	1
NEOPLASM MALIGNANT	0/129 (0%)	0	1/287 (0.3%)	1
NEOPLASM PROGRESSION	2/129 (1.6%)	2	0/287 (0%)	0
NON-SMALL CELL LUNG CANCER	0/129 (0%)	0	1/287 (0.3%)	1
SMALL CELL LUNG CANCER	1/129 (0.8%)	1	1/287 (0.3%)	1
SMALL CELL LUNG CANCER METASTATIC	0/129 (0%)	0	1/287 (0.3%)	1
TUMOUR NECROSIS	0/129 (0%)	0	1/287 (0.3%)	1
TUMOUR PAIN	1/129 (0.8%)	1	1/287 (0.3%)	2
Nervous system disorders
ATAXIA	0/129 (0%)	0	1/287 (0.3%)	1
CERVICAL CORD COMPRESSION	1/129 (0.8%)	1	0/287 (0%)	0
DEPRESSED LEVEL OF CONSCIOUSNESS	0/129 (0%)	0	2/287 (0.7%)	2
EMBOLIC STROKE	1/129 (0.8%)	1	0/287 (0%)	0
GENERALISED TONIC-CLONIC SEIZURE	0/129 (0%)	0	1/287 (0.3%)	1
HAEMORRHAGE INTRACRANIAL	0/129 (0%)	0	1/287 (0.3%)	1
HEADACHE	2/129 (1.6%)	2	1/287 (0.3%)	1
INTRACRANIAL PRESSURE INCREASED	1/129 (0.8%)	1	0/287 (0%)	0
INTRAVENTRICULAR HAEMORRHAGE	0/129 (0%)	0	1/287 (0.3%)	1
LOSS OF CONSCIOUSNESS	0/129 (0%)	0	1/287 (0.3%)	1
MEMORY IMPAIRMENT	1/129 (0.8%)	1	0/287 (0%)	0
NERVOUS SYSTEM DISORDER	1/129 (0.8%)	2	0/287 (0%)	0
SEIZURE	0/129 (0%)	0	2/287 (0.7%)	2
SOMNOLENCE	0/129 (0%)	0	1/287 (0.3%)	1
SYNCOPE	1/129 (0.8%)	1	1/287 (0.3%)	1
Psychiatric disorders
CONFUSIONAL STATE	2/129 (1.6%)	2	1/287 (0.3%)	1
MENTAL STATUS CHANGES	1/129 (0.8%)	1	0/287 (0%)	0
Renal and urinary disorders
ACUTE KIDNEY INJURY	0/129 (0%)	0	1/287 (0.3%)	1
RENAL FAILURE	1/129 (0.8%)	1	0/287 (0%)	0
URINARY RETENTION	0/129 (0%)	0	1/287 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
ACUTE LUNG INJURY	0/129 (0%)	0	1/287 (0.3%)	1
ACUTE RESPIRATORY DISTRESS SYNDROME	0/129 (0%)	0	1/287 (0.3%)	1
ACUTE RESPIRATORY FAILURE	0/129 (0%)	0	2/287 (0.7%)	2
ASTHMA	0/129 (0%)	0	1/287 (0.3%)	3
ATELECTASIS	0/129 (0%)	0	2/287 (0.7%)	2
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	0/129 (0%)	0	4/287 (1.4%)	5
CHRONIC RESPIRATORY FAILURE	0/129 (0%)	0	1/287 (0.3%)	1
DYSPNOEA	0/129 (0%)	0	16/287 (5.6%)	20
DYSPNOEA AT REST	0/129 (0%)	0	1/287 (0.3%)	1
HAEMOPTYSIS	0/129 (0%)	0	2/287 (0.7%)	2
HYPOXIA	2/129 (1.6%)	2	0/287 (0%)	0
INTERSTITIAL LUNG DISEASE	0/129 (0%)	0	2/287 (0.7%)	3
PLEURAL EFFUSION	0/129 (0%)	0	17/287 (5.9%)	17
PLEURISY	0/129 (0%)	0	1/287 (0.3%)	1
PNEUMONIA ASPIRATION	1/129 (0.8%)	1	1/287 (0.3%)	1
PNEUMOTHORAX	1/129 (0.8%)	1	3/287 (1%)	3
PULMONARY EMBOLISM	0/129 (0%)	0	3/287 (1%)	3
PULMONARY FIBROSIS	0/129 (0%)	0	1/287 (0.3%)	2
PULMONARY HAEMORRHAGE	0/129 (0%)	0	1/287 (0.3%)	1
RESPIRATORY DISTRESS	0/129 (0%)	0	2/287 (0.7%)	2
RESPIRATORY FAILURE	1/129 (0.8%)	1	4/287 (1.4%)	4
Skin and subcutaneous tissue disorders
ERYTHEMA	0/129 (0%)	0	1/287 (0.3%)	1
RASH MACULO-PAPULAR	0/129 (0%)	0	1/287 (0.3%)	1
Vascular disorders
DEEP VEIN THROMBOSIS	0/129 (0%)	0	1/287 (0.3%)	1
HYPOTENSION	0/129 (0%)	0	3/287 (1%)	3
SHOCK HAEMORRHAGIC	0/129 (0%)	0	1/287 (0.3%)	1
SUPERIOR VENA CAVA SYNDROME	1/129 (0.8%)	1	2/287 (0.7%)	2
Other (Not Including Serious) Adverse Events
	Topotecan		Rovalpituzumab Tesirine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	118/129 (91.5%)		245/287 (85.4%)
Blood and lymphatic system disorders
ANAEMIA	75/129 (58.1%)	136	42/287 (14.6%)	53
LEUKOPENIA	25/129 (19.4%)	80	4/287 (1.4%)	8
NEUTROPENIA	50/129 (38.8%)	136	14/287 (4.9%)	20
THROMBOCYTOPENIA	45/129 (34.9%)	94	39/287 (13.6%)	75
Cardiac disorders
PERICARDIAL EFFUSION	3/129 (2.3%)	3	56/287 (19.5%)	58
Gastrointestinal disorders
ABDOMINAL PAIN	11/129 (8.5%)	11	21/287 (7.3%)	25
CONSTIPATION	29/129 (22.5%)	36	33/287 (11.5%)	35
DIARRHOEA	25/129 (19.4%)	29	20/287 (7%)	24
NAUSEA	40/129 (31%)	58	65/287 (22.6%)	77
VOMITING	17/129 (13.2%)	20	30/287 (10.5%)	35
General disorders
ASTHENIA	21/129 (16.3%)	28	36/287 (12.5%)	47
CHEST PAIN	4/129 (3.1%)	4	18/287 (6.3%)	19
FATIGUE	35/129 (27.1%)	47	65/287 (22.6%)	85
OEDEMA PERIPHERAL	11/129 (8.5%)	14	51/287 (17.8%)	58
PYREXIA	6/129 (4.7%)	9	16/287 (5.6%)	18
Infections and infestations
URINARY TRACT INFECTION	8/129 (6.2%)	11	13/287 (4.5%)	13
Investigations
ALANINE AMINOTRANSFERASE INCREASED	1/129 (0.8%)	3	18/287 (6.3%)	31
ASPARTATE AMINOTRANSFERASE INCREASED	3/129 (2.3%)	4	20/287 (7%)	34
NEUTROPHIL COUNT DECREASED	12/129 (9.3%)	20	1/287 (0.3%)	1
PLATELET COUNT DECREASED	7/129 (5.4%)	13	9/287 (3.1%)	11
WEIGHT DECREASED	7/129 (5.4%)	7	18/287 (6.3%)	22
Metabolism and nutrition disorders
DECREASED APPETITE	35/129 (27.1%)	47	71/287 (24.7%)	87
HYPOALBUMINAEMIA	3/129 (2.3%)	3	17/287 (5.9%)	18
HYPOKALAEMIA	13/129 (10.1%)	13	18/287 (6.3%)	24
Musculoskeletal and connective tissue disorders
ARTHRALGIA	10/129 (7.8%)	11	16/287 (5.6%)	19
BACK PAIN	12/129 (9.3%)	12	21/287 (7.3%)	22
MYALGIA	7/129 (5.4%)	7	7/287 (2.4%)	8
Nervous system disorders
DYSGEUSIA	7/129 (5.4%)	8	6/287 (2.1%)	6
HEADACHE	11/129 (8.5%)	14	20/287 (7%)	21
PARAESTHESIA	7/129 (5.4%)	7	0/287 (0%)	0
Psychiatric disorders
INSOMNIA	9/129 (7%)	9	15/287 (5.2%)	17
Respiratory, thoracic and mediastinal disorders
COUGH	16/129 (12.4%)	19	42/287 (14.6%)	45
DYSPNOEA	25/129 (19.4%)	28	56/287 (19.5%)	69
EPISTAXIS	14/129 (10.9%)	16	9/287 (3.1%)	11
PLEURAL EFFUSION	5/129 (3.9%)	6	65/287 (22.6%)	72
Skin and subcutaneous tissue disorders
ALOPECIA	20/129 (15.5%)	24	3/287 (1%)	3
ERYTHEMA	0/129 (0%)	0	16/287 (5.6%)	22
PHOTOSENSITIVITY REACTION	0/129 (0%)	0	46/287 (16%)	60
RASH	1/129 (0.8%)	1	25/287 (8.7%)	34
Vascular disorders
HYPOTENSION	4/129 (3.1%)	6	16/287 (5.6%)	16

Limitations/Caveats

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Principal Investigators are NOT employed by the organization sponsoring the study.

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