Open Label Phase 2 Study of Tisotumab Vedotin for Locally Advanced or Metastatic Disease in Solid Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Seagen Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

13 Feb 2019 → ongoing

Decision date (initial)

2024-02-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-503812-34-00

EudraCT number

2017-005076-26

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Therapy, Pharmacokinetic, Safety, Others

Parts A, B, C, E: Evaluate antitumor activity of tisotumab vedotin as a single agent.
Part D, F, G: Evaluate antitumor activity of tisotumab vedotin in combination with pembrolizumab or with both pembrolizumab and platinum agent.

Secondary objectives 4

1. Parts A, B and C and E: -Evaluate preliminary antitumor activity of tisotumab vedotin as a single agent -Evaluate the safety and tolerability of tisotumab vedotin as a single agent
2. Parts D, F and G: -Evaluate preliminary antitumor activity of tisotumab vedotin in combination with pembrolizumab or with both pembrolizumab and a platinum agent -Evaluate the safety and tolerability of tisotumab vedotin in combination with pembrolizumab or with both pembrolizumab and carboplatin
3. Part D only: Evaluate preliminary safety and tolerability of tisotumab vedotin in combination with pembrolizumab and cisplatin, as measured by type, incidence, severity, seriousness, and relatedness of AEs
4. All Parts of Study: ● Assess pharmacokinetics (PK) and immunogenicity of tisotumab vedotin ● Evaluate stability and control of disease as measured by investigator-determined disease control rate (DCR) ● Evaluate durability of response as measured by investigator-determined duration of response (DOR) ● Evaluate timing of response as measured by investigator-determined time to response (TTR) ● Assess progression-free survival (PFS) as determined by investigator ●Assess survival as measured by OS

Conditions and MedDRA coding

Locally Advanced or Metastatic Disease in Solid Tumors

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Relapsed, locally-advanced or metastatic colorectal or pancreatic cancer, sqNSCLC, or SCCHN that has failed prior lines of systemic treatment as specified and which are not candidates for standard therapy. o Colorectal Cancer (closed to enrollment) o NSCLC(closed to enrollment) o Exocrine pancreatic adenocarcinoma(closed to enrollment) o SCCHN: Part C(closed to enrollment) Part E: Participants with SCCHN must have experienced disease progression on or after their most recent systemic therapy. Participants should have received no more than 1 or 2 systemic lines of therapy in the recurrent/metastatic setting as specified below. Maintenance therapy should not be counted as a separate line of therapy. Participants must have received one of the following: o A platinum-based regimen in combination with a PD-1/PD-L1 inhibitor in the first-line recurrent/metastatic setting. No more than 1 prior line of therapy in the recurrent/metastatic setting. o A platinum-based regimen in the first-line setting followed by a PD 1/PD L1 inhibitor (as monotherapy or in combination) in the second-line setting. No more than 2 prior lines of therapy in the recurrent/metastatic setting. o A PD-1/PD-L1 inhibitor in the first-line setting followed by a platinum therapy in the second-line setting. No more than 2 prior lines of therapy in the recurrent/metastatic setting. o Treatment with platinum therapy given as part of a multimodal therapy in the curative setting and experienced recurrence/progression within 6 months of the last dose followed by treatment with a PD-1/PD-L1 inhibitor (as monotherapy or in combination). No other lines of therapy prior to receiving study drug. China will participate in Part E only.
2. Measurable disease according to RECIST v1.1 as assessed by the investigator. o A minimum of one non-nodal lesion ≥10 mm in the longest diameter from a non-irradiated area. If target lesion(s) are located within previously irradiated area only, the patient can be enrolled only if there has been demonstrated progression in the "in field" lesion and upon approval of the sponsor's medical monitor. OR o Lymph node lesion ≥ 15mm in the shortest diameter from a non-irradiated area. o Part D, F and G: Part D is closed to enrollment. Part F and Part G will enroll only patients with SCCHN. · Patients with SCCHN must have received no previous systemic therapy for recurrent or metastatic disease with the exception of systemic therapy completed >6 months prior, if given as part of multimodal treatment for locally advanced disease in the curative setting. • Part D only: o Patients with NSCLC must have histologically or cytologically documented squamous cell NSCLC and must have received no previous systemic therapy for metastatic disease or radiation therapy to the lung that is > 30 Gy within 6 months of the first dose of study drug. o PD-L1 biomarker expression from IHC analysis should be available o Patients with SCCHN must have a CPS ≥1 to be eligible for the cohorts testing tisotumab vedotin in combination with pembrolizumab. Patients with sqNSCLC must have a TPS ≥1% to be enrolled to cohorts testing tisotumab vedotin in combination with pembrolizumab. • Part F only: o Patients must have CPS ≥1 by local PD-L1 IHC assay to be eligible for enrollment. Retrospective PD-L1 central testing is not required for enrollment. Patients must be able to submit a tissue sample for retrospective PD L1 testing. Tissue may be fresh biopsy or archival, collected within 2 years of Cycle 1 Day 1. •Part G only (cohort not opened): o Non-EU eligibility criteria: No CPS requirement for the cohort evaluating tisotumab vedotin in combination with pembrolizumab and carboplatin. o EU-specific eligibility criteria: Patients must have a CPS ≥1 by local PD L1 IHC assay. Retrospective PD-L1 central testing not required for enrollment. o Patients must be able to submit a tissue sample for retrospective PD-L1 testing. Retrospective PD-L1 central testing is not required for enrollment. Tissue may be fresh biopsy or archival, collected within 2 years of Cycle 1 Day 1. Other inclusion criteria can be found in Protocol.

Exclusion criteria 18

1. Primary neuroendocrine or sarcomatoid histologies. For SCCHN, participants may not have a primary site of nasopharynx (regardless of histology or salivary gland).
2. Uncontrolled tumor-related pain
3. Inflammatory lung disease, including moderate and severe asthma. Patients with chronic obstructive pulmonary disease are allowed if not requiring systemic steroids and long-term oxygen
4. Medications or treatment regimens: o Therapeutic anti-coagulation therapy is permitted If the patient is no longer being actively titrated for anti-coagulation. For oral anticoagulation therapy, patients must be on steady doses for at least 4 weeks prior to first dose of study drug. o Chronic prophylactic treatment with ASA (e.g., aspirin) in combination with other anti-coagulation therapy is prohibited. o Cumulative dose of corticosteroid ≥150 mg (prednisone or equivalent doses of corticosteroids) within 2 weeks of first tisotumab vedotin administration is prohibited.
5. Surgery/procedures: Major surgical procedure (defined as surgery requiring inpatient hospitalization of at least 48 hours) within 4 weeks or excisional biopsy within 7 days prior to first study drug administration. Patients who have planned major surgery during the treatment period must be excluded from the trial
6. Received a live vaccine within 30 days prior to first dose of trial treatment. Examples include in page 57 of Protocol. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed
7. Peripheral neuropathy Grade ≥2
8. Clinical symptoms or signs of gastrointestinal obstruction and requirement for parental hydration and/or nutrition
9. Prior therapy: o Prior treatment with MMAE-derived drugs. o At least 42 days must have elapsed from last administration of chemoradiotherapy or radiotherapy. Patients must have recovered from all radiation-related toxicities. Palliative radiotherapy within the previous 42 days may be allowed upon discussion with sponsor´s medical team/designee o Small molecules, chemotherapy, immunotherapy, biologics, experimental agents, or other antitumor therapy within 21 days prior to first administration of study drug. If underlying disease is progressing on treatment, patients may enroll within 21 days upon approval of sponsor's medical monitor. Participants must have recovered from all related toxicities
10. Seropositivity of human immunodeficiency virus; hepatitis B (defined as Hepatitis B surface antigen detected) or known active hepatitis C virus (defined as HCV RNA [qualitative] detected) infection. Part D, F, and G Only: Received prior therapy with an anti–PD-1, anti–PD-L1, or anti–PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor Other exclusion Criteria found in Protocol
11. Known past or current coagulation defects leading to an increased risk of bleeding; diffuse alveolar hemorrhage from vasculitis; known bleeding diathesis; ongoing major bleeding; trauma with increased risk of lifethreatening bleeding or history of severe head trauma or intracranial surgery within 8 weeks of trial entry
12. Clinically significant cardiac disease; medical history of congestive heart failure (Grade III or IV as classified by the New York Heart Association, see Appendix G); medical history of decreased cardiac ejection fraction of <45%.
13. Ophthalmological: Active ocular surface disease at baseline. Ocular evaluation confirmed by an ophthalmologist at screening. Patients with prior episode of cicatricial conjunctivitis or Steven Johnson syndrome (evaluated by the investigator) are ineligible. Please note that cataract is not considered active ocular surface disease for this protocol
14. Other cancer: known past or current malignancy other than inclusion diagnosis. Exceptions are malignancies with negligible risk of metastasis or death (e.g., 5-year overall survival ≥90%), such as non-invasive basal cell or squamous cell skin carcinoma, non-invasive, superficial bladder cancer, and ductal carcinoma in situ.
15. Leptomeningeal disease
16. Parts A, B, C and D: Tumor lesions invading, encasing, abutting, or involving critical anatomical sites, such as major blood vessels, (such as internal carotid artery, external carotid artery, pulmonary artery, etc) and mediastinal blood vessels. Mediastinal lymphadenopathy or invasion of mediastinal connective tissue is not an exclusion
17. Active inflammatory bowel disease including Crohn's disease and colitis ulcerosa
18. Ongoing, acute or chronic inflammatory skin disease that requires ongoing immunosuppressive therapy or systemic steroid therapy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Parts A, B, C and E: o Investigator-determined confirmed ORR as measured by RECIST v.1.1
2. Part D, F and G: o Investigator-determined confirmed ORR as measured by RECIST v.1.1

Secondary endpoints 3

1. Parts A, B, C and E: o Investigator-determined confirmed and unconfirmed ORR as measured by RECIST v.1.1 o Type, incidence, severity, seriousness, and relatedness of AEs
2. Part D, F and G: o Investigator-determined confirmed and unconfirmed ORR as measured by RECIST v.1.1 o Type, incidence, severity, seriousness, and relatedness of AEs
3. All parts of the Study: o Investigator-determined disease control rate (DCR) as measured by RECIST v1.1 o Investigator-determined time to response (TTR) as measured by RECIST v1.1 o Investigator-determined PFS as measured by RECIST v1.1 o Overall survival (OS) o Selected PK parameters for tisotumab vedotin, total antibody, MMAE o Incidence of anti-therapeutic antibodies (ATAs) to tisotumab vedotin

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Seagen Inc.

Sponsor organisation

Seagen Inc.

Address

21823 30th Drive Southeast

City

Bothell

Postcode

98021-3907

Country

United States

Scientific contact point

Organisation

Seagen Inc.

Contact name

Seagen Clinical Trial Information Support

Public contact point

Organisation

Seagen Inc.

Contact name

Seagen Clinical Trial Information Support

Third parties 2

Locations

4 EU/EEA countries · 29 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 32 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications