The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.

Clinical Trial Details

Geo Regions

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Other or Multiple Cancer Types

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Thoracic Cancer

Sigvotatug vedotin

Sigvotatug vedotin (SGN-B6A) is an investigational compound. Its safety and efficacy have not been established

A Phase 1 Study of SGN-B6A in Advanced Solid Tumors
Phase 1
NCT04389632

Active enrolling

Globe
Locations

United States, France, Spain, Switzerland, United Kingdom

Study design

Participant Group/Arm

EXPERIMENTAL: Part A: Dose escalation

sigvotatug vedotin monotherapy

Intervention/Treatment

DRUG: sigvotatug vedotin

Administered into the vein (IV; intravenously)

Participant Group/Arm

EXPERIMENTAL: Part B: Dose expansion

sigvotatug vedotin monotherapy

Intervention/Treatment

DRUG: sigvotatug vedotin

Administered into the vein (IV; intravenously)

Participant Group/Arm

EXPERIMENTAL: Part C: sigvotatug vedotin combination therapy in NSCLC, HNSCC, ESCC

sigvotatug vedotin + pembrolizumab +/- (carboplatin or cisplatin)

Intervention/Treatment

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

Participant Group/Arm

EXPERIMENTAL: Part D: sigvotatug vedotin combination therapy in 1L NSCLC

sigvotatug vedotin + pembrolizumab +/- (carboplatin)

Intervention/Treatment

DRUG: sigvotatug vedotin

Administered into the vein (IV; intravenously)

DRUG: pembrolizumab

200mg every 3 weeks or 400mg every 6 weeks, given by IV

DRUG: carboplatin

AUC 5 mg/mL per min every 3 weeks, given by IV

Participant Group/Arm

EXPERIMENTAL: Part D: sigvotatug vedotin combination therapy in 1L HNSCC

sigvotatug vedotin + pembrolizumab +/- (carboplatin or cisplatin)

Intervention/Treatment

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

Key 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).
  • Disease indication
    • 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 therap
  • 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) biop
  • 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.
  • 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

Key dates

Study start date
  • June 2020
Estimated primary completion date
  • October 2028

Key endpoints

Primary Outcome Measures
Outcome Measure

Number of participants with adverse events (AEs)

Measure Description

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.

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

Outcome Measure

Number of patients with laboratory abnormalities

Time Frame

Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years

Outcome Measure

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:
Outcome Measure

Confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator assessment

Measure Description

The proportion of participants with complete response (CR) or partial response (PR) which is subsequently confirmed as assessed according to RECIST v1.1.

Time Frame

Up to approximately 3 years

Outcome Measure

Duration of objective response (DOR) per RECIST v1.1 by investigator assessment

Measure Description

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

Time Frame

Up to approximately 3 years

Outcome Measure

Progression-free survival (PFS) per RECIST v1.1 by investigator assessment

Measure Description

The time from the start of any study treatment to the first documentation of PD, or death due to any cause

Time Frame

Up to approximately 3 years

Outcome Measure

Overall survival (OS)

Measure Description

The time from the start of any study treatment to the date of death due to any cause

Time Frame

Up to approximately 3 years

Outcome Measure

Area under the concentration-time curve (AUC)

Measure Description

Pharmacokinetic (PK) endpoint

Time Frame

Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years

Outcome Measure

Concentration at the end of infusion (Ceoi)

Measure Description

PK endpoint

Time Frame

Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years

Outcome Measure

Maximum observed concentration (Cmax)

Measure Description

PK endpoint

Time Frame

Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years

Outcome Measure

Time to maximum observed concentration (Tmax)

Measure Description

PK endpoint

Time Frame

Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years

Outcome Measure

Trough concentration (Ctrough)

Measure Description

PK endpoint

Time Frame

Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years

Outcome Measure

Apparent terminal elimination half-life (t1/2)

Measure Description

PK endpoint

Time Frame

Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years

Outcome Measure

Number of participants with antidrug antibodies (ADAs)

Time Frame

Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years

Number of participants

824

Collaborators and investigators

Sponsor: Seagen Inc.

Collaborator: None

This information is current as of May 7th 2024.