A Study of Ladiratuzumab Vedotin in Advanced Solid Tumors

Sponsor

Seagen Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04032704

Collaborator

(none)

264

Enrollment

Locations

Arm

69.7

Anticipated Duration (Months)

4.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This trial will study ladiratuzumab vedotin (LV) to find out if it works to treat different types of solid tumors. It will also find out what side effects may occur. A side effect is anything the drug does besides treating cancer.

Condition or Disease	Intervention/Treatment	Phase
Small Cell Lung Cancer Non-small Cell Lung Cancer, Squamous Non-small Cell Lung Cancer, Non-squamous Head and Neck Squamous Cell Carcinoma Esophageal Squamous Cell Carcinoma Gastric Adenocarcinoma Gastroesophageal Junction Adenocarcinoma Prostate Cancer Melanoma	Drug: ladiratuzumab vedotin	Phase 2

Detailed Description

This trial is designed to assess the antitumor activity, safety, and tolerability of LV for the treatment of solid tumors. Participants with the following advanced solid tumors will be enrolled:

Cohort 1: small cell lung cancer (SCLC) Cohort 2: non-small cell lung cancer-squamous (NSCLC-squamous) Cohort 3: non-small cell lung cancer-nonsquamous (NSCLC-nonsquamous) Cohort 4: head and neck squamous cell carcinoma (HNSCC) Cohort 5: esophageal squamous cell carcinoma (esophageal-squamous) Cohort 6: gastric and gastroesophageal junction (GEJ) adenocarcinoma Cohort 7: castration-resistant prostate cancer (CRPC) Cohort 8: melanoma

Participants will continue to receive study treatment until disease progression, unacceptable toxicity, investigator decision, consent withdrawal, study termination by the sponsor, pregnancy, or death, whichever comes first.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

264 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Open-Label Phase 2 Study of Ladiratuzumab Vedotin (LV) for Unresectable Locally Advanced or Metastatic Solid Tumors

Actual Study Start Date :

Oct 9, 2019

Anticipated Primary Completion Date :

May 31, 2024

Anticipated Study Completion Date :

Jul 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ladiratuzumab Vedotin SGN-LIV1A monotherapy	Drug: ladiratuzumab vedotin Intravenous (into the vein; IV) infusion Other Names: SGN-LIV1A

Arm

Intervention/Treatment

Experimental: Ladiratuzumab Vedotin

SGN-LIV1A monotherapy

Drug: ladiratuzumab vedotin

Intravenous (into the vein; IV) infusion

Other Names:

SGN-LIV1A

Outcome Measures

Primary Outcome Measures

Confirmed objective response rate (ORR) as determined by investigator according to RECIST v1.1 [Up to approximately 1 year]
Confirmed ORR is defined as the proportion of participants who achieve a confirmed complete response (CR) or partial response (PR) according to RECIST v1.1 as assessed by the investigator.
Prostate-specific antigen (PSA) response rate as determined by investigator according to Prostate Cancer Clinical Trials Working Group 3 criteria (Cohort 7 only) [Up to approximately 1 year]
Confirmed PSA response rate is defined as the proportion of participants with a reduction from baseline PSA level of at leat 50%, measured twice ≥3 weeks apart

Secondary Outcome Measures

Number of participants with adverse events (AEs) [Up to approximately 1 year]
Disease control rate (DCR) as determined by investigator according to RECIST v1.1 [Up to approximately 1 year]
DCR is defined as the proportion of participants who achieve a confirmed CR or PR, or meet the stable disease (SD) criteria at least once after start of study treatment at a minimum interval of 5 weeks.
Duration of response (DOR) as determined by investigator according to RECIST v1.1 [Up to approximately 1 year]
DOR is defined as the time from the first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of progressive disease (PD) or death due to any cause, whichever comes first.
PSA-DOR as determined by investigator assessment (Cohort 7 only) [Up to approximately 1 year]
PSA-DOR is defined as the time from the first documentation of PSA response to the first documentation of PSA progression or death, whichever comes first
Progression-free survival (PFS) as determined by investigator according to RECIST v1.1 [Up to approximately 1 year]
Progression-free survival (PFS) is defined as the time from the start of study treatment to the first documentation of PD or death due to any cause, whichever comes first.
PSA-PFS as determined by investigator assessment (Cohort 7 only) [Up to approximately 1 year]
PSA-PFS is defined as the time from the start of study treatment to first occurrence of PSA progression or death, whichever comes first
Overall survival (OS) [Up to approximately 1 year]
OS is defined as the time from the start of study treatment to date of death due to any cause.
Maximum observed concentration (Cmax) [Up to approximately 1 year]
Pharmacokinetic (PK) endpoint of LV
Area under the concentration-time curve (AUC) [Up to approximately 1 year]
PK endpoint of LV
Incidence of antitherapeutic antibodies (ATAs) to LV [Up to approximately 1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

All Cohorts
Measurable disease according to RECIST v1.1 as assessed by the investigator
Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1
Cohort 1: SCLC
Must have extensive stage disease
Must have disease progression during or following prior platinum-based systemic chemotherapy for extensive stage disease;
No more than 1 prior line of cytotoxic chemotherapy for extensive disease stage
No more than 1 prior line of cytotoxic chemotherapy for extensive disease stage
May have received prior anti-PD(L)1 therapy
Cohort 2: NSCLC-squamous
Must have unresectable locally advanced or metastatic disease
Must have disease progression during or following systemic therapy
Participants must have progressed during or after a platinum-based combination therapy administered for the treatment of metastatic disease, OR
Participants must have progressed within 6 months of last dose of platinum-based adjuvant, neoadjuvant, or definitive chemotherapy, or concomitant chemoradiation regimen for early stage or locally advanced stage disease.
Participants with known epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), reactive oxygen species (ROS), BRAF, or other actionable mutations are not eligible
No more than 1 prior line of cytotoxic chemotherapy for their advanced disease
Must have received prior anti-PD(L)1 therapy, unless contraindicated
Cohort 3: NSCLC-nonsquamous
Must have unresectable locally advanced or metastatic disease
Must have disease progression during or following systemic therapy
Participants must have progressed during or after a platinum-based combination therapy administered for the treatment of metastatic disease, OR
Participants must have progressed within 6 months of last dose of platinum-based adjuvant, neoadjuvant, or definitive chemotherapy, or concomitant chemoradiation regimen for early stage or locally advanced state disease.
Participants with known EGFR, ALK, ROS, BRAF, tropomyosin receptor kinase (TRK), or other actionable mutations are not eligible
Must have had prior platinum-based chemotherapy
No more than 1 prior line of cytotoxic chemotherapy for their advanced disease
Must have received prior anti-PD(L)1 therapy, unless contraindicated
Cohort 4: HNSCC
Must have unresectable locally recurrent or metastatic disease
Must have disease progression during or following prior line of systemic therapy
Disease progression after treatment with a platinum-containing regimen for recurrent/metastatic disease; or
Recurrence/progression within 6 months of last dose of platinum therapy given as part of a multimodal therapy in the curative setting
No more than 1 line of cytotoxic chemotherapy for their advanced disease
May have received prior anti-PD(L)1 therapy, unless contraindicated
Cohort 5: esophageal-squamous
Must have unresectable locally advanced or metastatic disease
Must have disease progression during or following systemic therapy
Must have had prior platinum-based chemotherapy
No more than 1 line of cytotoxic chemotherapy for their advanced disease
Cohort 6: gastric and GEJ adenocarcinoma
Must have unresectable locally advanced or metastatic disease
Must have received prior platinum-based therapy
Must have disease progression during or following systemic therapy
Participants with known human epidermal growth factor receptor 2 (HER2) overexpression must have received prior HER2-targeted therapy
No more than 1 line of prior cytotoxic chemotherapy for their advanced disease
Participants may have received prior anti-PD(L)1 therapy, unless contraindicated
Cohort 7: CRPC
Must have histologically or cytologically confirmed adenocarcinoma of the prostate
Participants with components of small cell of neuroendocrine histology are excluded
Must have metastatic castration-resistant disease
Must have been ≥28 days between cessation of androgen receptor-targeted therapy and start of study treatment
Must have received no more than 1 prior line of androgen receptor-targeted therapy for metastatic castration-sensitive prostate cancer or CRPC
No prior cytotoxic chemotherapy in the metastatic CRPC setting
For participants who received cytotoxic chemotherapy in CSPC, at least 6 months must have elapsed between last dose of chemotherapy and start of study treatment
No more than 1 prior line of cytotoxic chemotherapy for CSPC
Participants with measurable and non-measurable disease are eligible if the following criteria are met:
A minimum starting PSA level ≥1.0 ng/mL
Participants with measurable soft tissue disease must have evidence of measurable soft tissue disease according to PCWG3 criteria.
Participants with non-measurable disease must have documented rising PSA levels or appearance of new lesion according to PCWG3
Participants with known breast cancer gene (BRCA) mutations are excluded
No prior radioscope therapy or radiotherapy to ≥30% of bone marrow
Cohort 8: Melanoma
Must have histologically or cytotoxically confirmed cutaneous malignant melanoma
Participants with mucosal, acral, or uveal melanoma are excluded
Must have locally advanced unresectable or metastatic stage disease
Must have measurable disease
Must have progressive disease following anti-PD(L)1 therapy

Exclusion Criteria

Active concurrent malignancy or a previous malignancy within the past 3 years
Any anticancer therapy within 3 weeks of starting study treatment. Participants who are/were on adjuvant hormonal therapy for the treatment of malignancies with negligible risk of metastases are eligible.
Known active central nervous system lesions
Active viral, bacterial, or fungal infection requiring systemic treatment within 7 days prior to the first dose of LV
Any ongoing clinically significant toxicity associated with prior treatment (Grade 2 or higher)
Ongoing sensory or motor neuropathy of Grade ≥2
Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with congestive heart failure
Has received prior radiotherapy within 2 weeks of start of study treatment
Has received a live vaccine within 30 days of the planned start of study therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ironwood Cancer & Research Centers - Chandler	Chandler	Arizona	United States	85224
2	Adventist Health White Memorial	Los Angeles	California	United States	90033
3	Saint Joseph Heritage Medical Group	Santa Rosa	California	United States	95403
4	Eastern CT Hematology and Oncology Associates	Norwich	Connecticut	United States	06360
5	GenesisCare USA	Jacksonville	Florida	United States	32204
6	AdventHealth Cancer Institute	Orlando	Florida	United States	32804
7	IACT Health	Columbus	Georgia	United States	31904
8	Northwestern University	Chicago	Illinois	United States	60611
9	Decatur Memorial Hospital - Illinois	Decatur	Illinois	United States	62526
10	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana	United States	46804
11	University of Maryland	Baltimore	Maryland	United States	21201
12	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
13	HealthPartners Institute	Saint Louis Park	Minnesota	United States	55416
14	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89169
15	Valley Hospital, The / Luckow Pavilion	Paramus	New Jersey	United States	07652
16	San Juan Oncology Associates	Farmington	New Mexico	United States	87401
17	Weill Cornell Medicine	New York	New York	United States	10065
18	Stony Brook University Cancer Center	Stony Brook	New York	United States	11794-7263
19	FirstHealth of the Carolinas	Pinehurst	North Carolina	United States	28374
20	Gabrail Cancer Center Research, LLC	Canton	Ohio	United States	44718
21	Providence Portland Medical Center	Portland	Oregon	United States	97213
22	Saint Francis Hospital / Bon Secours - South Carolina	Greenville	South Carolina	United States	29601
23	Erlanger Oncology and Hematology	Chattanooga	Tennessee	United States	37403
24	Tennessee Oncology-Nashville/Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
25	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas	United States	79410
26	UT Health East Texas Hope Cancer Center	Tyler	Texas	United States	75701
27	Carbone Cancer Center / University of Wisconsin	Madison	Wisconsin	United States	53792
28	Flinders Medical Centre	Bedford Park	Other	Australia	5042
29	Townsville Cancer Center	Douglas	Other	Australia	4814
30	Peninsula and South East Oncology	Frankston	Other	Australia	3199
31	Central Coast Local Health District (Gosford and Wyong Hospitals)	Gosford	Other	Australia	2250
32	Royal Hobart Hospital	Hobart	Other	Australia	7000
33	Cabrini	Malvern	Other	Australia	3144
34	St Vincents Hospital Sydney	Sydney	Other	Australia	2010
35	Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi	Bologna	Other	Italy	40138
36	Azienda Ospedaliero Universitaria Careggi	Florence	Other	Italy	50134
37	ASL 3 Genovese Villa Scassi Hospital	Genova	Other	Italy	16125
38	San Luca Hospital	Lucca	Other	Italy	55100
39	Irccs Irst	Meldola	Other	Italy	47014
40	Istituto Europeo di Oncologia	Milano	Other	Italy	20141
41	Niguarda Ca' Granda Hospital	Milan	Other	Italy	20162
42	San Gerardo di Monza Hospital	Monza	Other	Italy	20900
43	Istituto Nazionale Tumori IRCCS Fondazione G. Pascale	Napoli	Other	Italy	80131
44	Policlinico Universitario Agostino Gemelli	Rome	Other	Italy	00168
45	AOUS Policlininico Le Scotte	Siena	Other	Italy	53100
46	Dong-A University Hospital	Busan	Other	Korea, Republic of	49201
47	Chonnam National University Hwasun Hospital	Hwasun	Other	Korea, Republic of	519-763
48	Seoul National University Bundang Hospital	Seongnam-si	Other	Korea, Republic of	13605
49	Seoul National University Hospital	Seoul	Other	Korea, Republic of	03080
50	Severance Hospital, Yonsei University Health System	Seoul	Other	Korea, Republic of	03722
51	Samsung Medical Center	Seoul	Other	Korea, Republic of	06351
52	Seoul National University Boramae Medical Center	Seoul	Other	Korea, Republic of	07671
53	Korea University Guro Hospital	Seoul	Other	Korea, Republic of	152-703/08308
54	St. Vincent's Hospital, The Catholic University of Korea	Suwon-si	Other	Korea, Republic of	16247
55	Ajou University Hospital	Suwon-si	Other	Korea, Republic of	16499
56	Taichung Veterans General Hospital	Taichung	Other	Taiwan	40705
57	National Cheng-Kung University Hospital	Tainan	Other	Taiwan	70403
58	National Taiwan University Hospital	Taipei	Other	Taiwan	10002
59	Taipei Medical University Hospital	Taipei	Other	Taiwan	110
60	The Beatson West of Scotland Cancer Centre	Glasgow	Other	United Kingdom	G12 0YN
61	The Royal Marsden Hospital	London	Other	United Kingdom	SW3 6JJ
62	Sarah Cannon Research Institute UK	London	Other	United Kingdom	W1G 6AD
63	UCL Cancer Institute	London	Other	United Kingdom	WC1E6DD
64	The Christie NHS Foundation Trust	Manchester	Other	United Kingdom	M20 4BX
65	The Royal Marsden Hospital (Surrey)	Sutton	Other	United Kingdom	SM2 5PT