Recruiting NCT04389632

A Study of Sigvotatug Vedotin in Advanced Solid Tumors

Phase I Interventional Carcinoma, Non-Small Cell Lung Squamous Cell Carcinoma of Head and Neck HER2 Negative Breast Neoplasms Esophageal Squamous Cell Carcinoma

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: sigvotatug vedotin, pembrolizumab, cisplatin, carboplatin.
Who it may be relevant to: Registry conditions: Carcinoma, Non-Small Cell Lung, Squamous Cell Carcinoma of Head and Neck, HER2 Negative Breast Neoplasms, Esophageal Squamous Cell Carcinoma. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, France, South Korea, Spain, Switzerland +2
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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Official title

A Phase 1 Study of Sigvotatug Vedotin in Advanced Solid Tumors

Overview

This trial will look at a drug called sigvotatug vedotin (SGN-B6A) alone and with pembrolizumab, with or without chemotherapy, to find out whether it is safe for people who have solid tumors. It will study sigvotatug vedotin to find out what its side effects are. A side effect is anything the drug does besides treating cancer. It will also study whether sigvotatug vedotin works to treat solid tumors. The study will have four parts. * Part A of the study will find out how much sigvotatug vedotin should be given to participants. * Part B will use the dose found in Part A to find out how safe sigvotatug vedotin is and if it works to treat solid tumors. * Part C of the study will find out how safe sigvotatug vedotin is in combination with these other drugs. * Part D will include people who have not received treatment. This part of the study will find out how safe sigvotatug vedotin is in combination with these other drugs and if these combinations work to treat solid tumors. * In Parts C and D, participants will receive sigvotatug vedotin with either: * Pembrolizumab or, * Pembrolizumab and carboplatin, or * Pembrolizumab and cisplatin.

Interventions

Drug sigvotatug vedotin
Administered into the vein (IV; intravenously)
Drug pembrolizumab
200mg every 3 weeks or 400mg every 6 weeks, given by IV
Drug cisplatin
75 mg/m2 every 3 weeks, given by IV
Drug carboplatin
AUC 5 mg/mL per min every 3 weeks, given by IV

Primary outcome measures

Number of participants with adverse events (AEs) [Time frame: Through 30-37 days following last dose of sigvotatug vedotin. For participants receiving pembrolizumab up to 90 days after last dose of pembrolizumab; up to 3 years]
Number of patients with laboratory abnormalities [Time frame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years]
Number of participants with dose-limiting toxicities (DLTs) [Time frame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years]

Secondary outcome measures (11)

Confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator assessment [Time frame: Up to approximately 3 years]
Duration of objective response (DOR) per RECIST v1.1 by investigator assessment [Time frame: Up to approximately 3 years]
Progression-free survival (PFS) per RECIST v1.1 by investigator assessment [Time frame: Up to approximately 3 years]
Overall survival (OS) [Time frame: Up to approximately 3 years]
Area under the concentration-time curve (AUC) [Time frame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years]
Concentration at the end of infusion (Ceoi) [Time frame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years]
Maximum observed concentration (Cmax) [Time frame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years]
Time to maximum observed concentration (Tmax) [Time frame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years]
Trough concentration (Ctrough) [Time frame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years]
Apparent terminal elimination half-life (t1/2) [Time frame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years]
Number of participants with antidrug antibodies (ADAs) [Time frame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years]

Eligibility criteria

Inclusion criteria

Disease indication

Participants must have histologically or cytologically confirmed metastatic or unresectable solid malignancy within one of the tumor types listed below (dependent on study part).

Non-small cell lung cancer (NSCLC)
Head and neck squamous cell cancer (HNSCC)
Advanced HER2-negative breast cancer
Esophageal squamous cell carcinoma (ESCC)
Esophageal/Gastro-esophageal junction adenocarcinoma (EAC/GEJ)
Cutaneous squamous cell cancer (cSCC)
Exocrine pancreatic adenocarcinoma
Bladder cancer
Cervical cancer
Gastric cancer
High grade serous ovarian cancer (HGSOC)
Part A only: Participants must have disease that is relapsed or refractory or be intolerant to standard-of-care therapies and should have no appropriate standard-of-care therapeutic options.
Part B only: Participants must have disease that is relapsed or refractory or be intolerant to standard-of-care therapies. Participants must have received platinum-based therapy and a PD-1/PD-(L)1 inhibitor, if applicable and available.
Part C only: For pembrolizumab combination cohorts, participants must be eligible for pembrolizumab per local standard of care. For pembrolizumab with cisplatin or carboplatin, participants must be eligible for both pembrolizumab and the platinum agent per local standard of care. Participants must be treatment naïve for locally advanced or metastatic systemic therapy (prior definitively intended or \[neo\]adjuvant therapy is allowed).
Part D only: Participants must be treatment naïve for locally advanced or metastatic systemic therapy.
Participants enrolled in the following study parts should have a tumor site accessible for biopsy and agree to biopsy as follows:

Disease-specific expansion cohorts (Part B and Part D): A baseline fresh tumor biopsy is required. An archival biopsy collected within 90 days prior to first dose of study drug may be used.
Biology expansion cohort: pretreatment biopsy and on-treatment (Cycle 1) biopsy
An Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Measurable disease per the RECIST v1.1 at baseline

Exclusion criteria

History of another malignancy within 3 years before first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death.
Known active central nervous system metastases. Participants with previously treated brain metastases may participate provided they:

are clinically stable for at least 4 weeks prior to study entry after brain metastasis treatment,
have no new or enlarging brain metastases, and
are off of corticosteroids prescribed for symptoms associated with brain metastases for at least 7 days prior to first dose of study drug.
In Part D, participants with untreated, asymptomatic CNS metastases smaller than 1 cm may be enrolled without definitive treatment as long as they have no neurological symptoms, no or minimal surrounding edema, and no requirements for corticosteroids.
Carcinomatous meningitis
Previous receipt of an MMAE-containing agent or an agent targeting integrin beta-6
Pre-existing neuropathy Grade 1 or greater per the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0) for Parts C and D cohorts with cisplatin or carboplatin; Grade 2 or greater per the NCI CTCAE v5.0 for all other cohorts
Any uncontrolled Grade 3 or higher (per NCI CTCAE v5.0) viral, bacterial, or fungal infection within 2 weeks prior to the first dose of sigvotatug vedotin.

Routine antimicrobial prophylaxis is permitted
Grade ≥3 pulmonary disease unrelated to underlying malignancy. This includes clinically severe pulmonary function compromise resulting from clinically significant pulmonary illnesses
Part C and D: Prior therapy with a PD-1 inhibitor, anti-PD-(L)1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor and was discontinued from that treatment due to a Grade 3 or higher immune-mediated adverse event (IMAE).
History of noninfectious interstitial lung disease (ILD) or pneumonitis that required steroids, current ILD or pneumonitis, or suspected ILD or pneumonitis that cannot be ruled out by imaging at screening
Known diffusing capacity of the lung for carbon monoxide (DLCO; adjusted for hemoglobin) <50% predicted
Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: N/A
Model: Sequential
Masking: Open label
Primary purpose: Treatment