A Study of Sigvotatug Vedotin in Advanced Solid Tumors
- Conditions
- Squamous Cell Carcinoma of Head and NeckHER2 Negative Breast NeoplasmsCutaneous Squamous Cell CancerExocrine Pancreatic AdenocarcinomaUterine Cervical NeoplasmsCarcinoma, Non-Small Cell LungEsophageal Squamous Cell CarcinomaUrinary Bladder NeoplasmsEsophageal AdenocarcinomaGastroesophageal Junction Adenocarcinoma
- Interventions
- Registration Number
- NCT04389632
- Lead Sponsor
- Seagen, a wholly owned subsidiary of Pfizer
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1006
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Disease indication
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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)
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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.
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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.
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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).
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Part D only: Participants must be treatment naïve for locally advanced or metastatic systemic therapy.
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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
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An Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
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Measurable disease per the RECIST v1.1 at baseline
Exclusion Criteria
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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.
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Carcinomatous meningitis
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Previous receipt of an MMAE-containing agent or an agent targeting integrin beta-6
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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
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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
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Grade ≥3 pulmonary disease unrelated to underlying malignancy. This includes clinically severe pulmonary function compromise resulting from clinically significant pulmonary illnesses
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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).
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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
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Known diffusing capacity of the lung for carbon monoxide (DLCO; adjusted for hemoglobin) <50% predicted
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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.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A: Dose escalation sigvotatug vedotin sigvotatug vedotin monotherapy Part B: Dose expansion sigvotatug vedotin sigvotatug vedotin monotherapy Part C: sigvotatug vedotin combination therapy in NSCLC, HNSCC, ESCC sigvotatug vedotin sigvotatug vedotin + pembrolizumab +/- (carboplatin or cisplatin) Part C: sigvotatug vedotin combination therapy in NSCLC, HNSCC, ESCC pembrolizumab sigvotatug vedotin + pembrolizumab +/- (carboplatin or cisplatin) Part C: sigvotatug vedotin combination therapy in NSCLC, HNSCC, ESCC cisplatin sigvotatug vedotin + pembrolizumab +/- (carboplatin or cisplatin) Part C: sigvotatug vedotin combination therapy in NSCLC, HNSCC, ESCC carboplatin sigvotatug vedotin + pembrolizumab +/- (carboplatin or cisplatin) Part D: sigvotatug vedotin combination therapy in 1L NSCLC sigvotatug vedotin sigvotatug vedotin + pembrolizumab +/- (carboplatin) Part D: sigvotatug vedotin combination therapy in 1L NSCLC pembrolizumab sigvotatug vedotin + pembrolizumab +/- (carboplatin) Part D: sigvotatug vedotin combination therapy in 1L NSCLC carboplatin sigvotatug vedotin + pembrolizumab +/- (carboplatin) Part D: sigvotatug vedotin combination therapy in 1L HNSCC sigvotatug vedotin sigvotatug vedotin + pembrolizumab +/- (carboplatin or cisplatin) Part D: sigvotatug vedotin combination therapy in 1L HNSCC pembrolizumab sigvotatug vedotin + pembrolizumab +/- (carboplatin or cisplatin) Part D: sigvotatug vedotin combination therapy in 1L HNSCC cisplatin sigvotatug vedotin + pembrolizumab +/- (carboplatin or cisplatin) Part D: sigvotatug vedotin combination therapy in 1L HNSCC carboplatin sigvotatug vedotin + pembrolizumab +/- (carboplatin or cisplatin)
- Primary Outcome Measures
Name Time Method Number of participants with dose-limiting toxicities (DLTs) Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years Number of participants with adverse events (AEs) 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 Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
Number of patients with laboratory abnormalities Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years
- Secondary Outcome Measures
Name Time Method Overall survival (OS) Up to approximately 3 years The time from the start of any study treatment to the date of death due to any cause
Maximum observed concentration (Cmax) Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years PK endpoint
Trough concentration (Ctrough) Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years PK endpoint
Number of participants with antidrug antibodies (ADAs) Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years Area under the concentration-time curve (AUC) Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years Pharmacokinetic (PK) endpoint
Concentration at the end of infusion (Ceoi) Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years PK endpoint
Time to maximum observed concentration (Tmax) Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years PK endpoint
Duration of objective response (DOR) per RECIST v1.1 by investigator assessment Up to approximately 3 years 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 to death due to any cause
Confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator assessment Up to approximately 3 years The proportion of participants with complete response (CR) or partial response (PR) which is subsequently confirmed as assessed according to RECIST v1.1.
Progression-free survival (PFS) per RECIST v1.1 by investigator assessment Up to approximately 3 years The time from the start of any study treatment to the first documentation of PD, or death due to any cause
Apparent terminal elimination half-life (t1/2) Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years PK endpoint
Trial Locations
- Locations (120)
Alaska Oncology and Hematology
🇺🇸Anchorage, Alaska, United States
Highlands Oncology Group
🇺🇸Springdale, Arkansas, United States
Providence Medical Foundation
🇺🇸Fullerton, California, United States
Providence St. Jude Medical Center Virginia K Crosson and Infusion Center
🇺🇸Fullerton, California, United States
Cancer and Blood Research Center, LLC
🇺🇸Los Alamitos, California, United States
Cancer and Blood Specialty Clinic
🇺🇸Los Alamitos, California, United States
Ronald Reagan UCLA Medical Center
🇺🇸Los Angeles, California, United States
UCLA Department of Medicine-Hematology/Oncology
🇺🇸Los Angeles, California, United States
UCLA Department of Medicine - Hematology & Oncology
🇺🇸Santa Monica, California, United States
Cancer AND Blood Specialty Clinic
🇺🇸Torrance, California, United States
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