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

Cancer Categories

Gastrointestinal (GI),Head and Neck,Lung,Skin

Karmanos Trial ID

2023-029

NCT ID

NCT03485209

Age Group

Adult

Scope

National

Phase

Phase II

Principal Investigator

Ammar
Sukari, M.D.
Oncology - Medical View Profile

Objective:

Primary Objectives:

Parts A, B, and C: Evaluate antitumor activity of tisotumab vedotin as a single agent as measured by investigator-determined confirmed objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Part D: Evaluate antitumor activity of tisotumab vedotin in combination with pembrolizumab or with both pembrolizumab and carboplatin, as measured by investigator-determined confirmed objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Secondary Objectives:

Parts A, B, and C:

Evaluate preliminary antitumor activity of tisotumab vedotin as a single agent, as measured by confirmed and unconfirmed ORR
Evaluate the safety and tolerability of tisotumab vedotin as a single agent, as measured by type, incidence, severity, seriousness, and relatedness of adverse events (AEs)

Part D:

Evaluate preliminary antitumor activity of tisotumab vedotin in combination with pembrolizumab or with both pembrolizumab and a platinum agent (carboplatin or cisplatin), as measured by confirmed and unconfirmed ORR, per RECIST v1.1
Evaluate the safety and tolerability of tisotumab vedotin in combination with pembrolizumab or with both pembrolizumab and carboplatin, as measured by type, incidence, severity, seriousness, and relatedness of adverse events (AEs)
Evaluate preliminary safety and tolerability of tisotumab vedotin in combination with pembrolizumab and cisplatin

All Parts of Study:

Assess pharmacokinetics (PK) and immunogenicity of tisotumab vedotin
Evaluate stability and control of disease as measured by disease control rate (DCR)
Evaluate durability of response as measured by duration of response (DOR)
Evaluate timing of response as measured by time to response (TTR)
Assess progression-free survival (PFS)
Assess survival as measured by overall survival (OS)

Additional Objectives:

Assess Tissue Factor (TF) expression-response relationship
Assess biomarkers of biological activity and resistance and predictive biomarkers of response
Evaluate patient reported outcomes (PRO) and health-related quality of life (HRQOL) for Part D only

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Eligibility

Inclusion Criteria:

Parts A, B, and C

Relapsed, locally-advanced or metastatic colorectal or pancreatic cancer, sqNSCLC, or HNSCC participants who are not candidates for standard therapy.
All participants must have experienced disease progression on or after their most recent systemic therapy.
Colorectal cancer (closed to enrollment): participants must have received prior therapy with each of following agents, if eligible: a fluoropyrimidine, oxaliplatin, irinotecan, and/or bevacizumab. Participants should have received no more than 3 systemic regimens in the metastatic setting.
sqNSCLC (closed to enrollment): Participants with NSCLC must have predominant squamous histology. Participants must have received prior therapy with a platinum-based treatment and a checkpoint inhibitor (CPI), if eligible. Participants should have received no more than 3 lines of systemic therapy in the metastatic setting.

Participants eligible for a tyrosine kinase inhibitor should have received such therapy. These participants should have received no more than 4 lines of systemic therapy in the metastatic setting.

Exocrine pancreatic adenocarcinoma (closed to enrollment): Participants with exocrine pancreatic adenocarcinoma must have predominant adenocarcinoma histology. Participants must have received prior therapy with a gemcitabine-based or 5FU-based regimen, if eligible, and should have received no more than 1 systemic regimen in the unresectable or metastatic setting.
HNSCC (closed to enrollment): Participants with HNSCC in Part C must have received prior therapy with a platinum-based regimen and/or a checkpoint inhibitor (CPI), if eligible, and must have experienced disease progression following such therapy. Participants should have received no more than 3 systemic lines of therapy in the recurrent or metastatic setting.

Part E

Participants with HNSCC 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. Participants must have received a platinum-based regimen and a PD-(L)1 inhibitor.

Parts D, F, and G

Part D is closed to enrollment. Part F and Part G will enroll only participants with HNSCC.
Participants with HNSCC must have received no previous systemic therapy in the recurrent or metastatic disease setting.
Part D only

Participants 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 treatment.
PD-L1 biomarker expression as determined by a PD-L1 IHC assay should be available

Part F only

Participants must have CPS ≥1 by local PD-L1 IHC assay to be eligible for enrollment. Participants 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

Non-EU eligibility criteria: No CPS requirement for the cohort evaluating tisotumab vedotin in combination with pembrolizumab and carboplatin.
EU-specific eligibility criteria: Participants must have a CPS ≥1 by local PD-L1 IHC assay.
Participants 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.

Baseline measurable disease as measured by RECIST v1. 1.
Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.

Exclusion Criteria:

Participants with primary neuroendocrine or sarcomatoid histologies. For HNSCC, participants may not have a primary site of nasopharynx or salivary gland.
Active bleeding conditions
Ocular surface disease at the time of enrollment (Note: cataract is not considered active ocular surface disease for this protocol)
Other cancer: known past or current malignancy other than inclusion diagnosis.
Uncontrolled tumor-related pain
Inflammatory lung disease. Participants with pulmonary disease are allowed if systemic steroids and long-term oxygen are not required
Peripheral neuropathy greater than or equal to Grade 2
Active brain metastasis
Ongoing clinically significant toxicity associated with prior treatment (including radiotherapy or surgery).

Locations

Karmanos Cancer Institute - Detroit Headquarters

4100 John R
Detroit, MI 48201
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Phone: 800-527-6266

Karmanos Cancer Institute at Weisberg Cancer Center - Farmington Hills

31995 Northwestern Hwy
Farmington Hills, MI 48334
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Phone: 800-527-6266

Applicable Disease Site

Therapies, Drugs, Devices