Clinical trial NCT05194072: A Study of Felmetatug Vedotin/SGN-B7H4V in Advanced Solid Tumors
Official title: A Phase 1 Study of Felmetatug Vedotin/SGN-B7H4V in Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Ovarian Neoplasms
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Triple Negative Breast Neoplasms
HER2 Negative Breast Neoplasms
Hormone Receptor Positive Breast Neoplasms
Endometrial Neoplasms
Carcinoma, Non-Small-Cell Lung
Cholangiocarcinoma
Gallbladder Carcinoma
Adenoid Cystic Carcinoma
Keywords: High-grade serous epithelial ovarian cancer
Primary peritoneal cancer
Fallopian tube cancer
HER2-negative breast cancer
HR positive breast cancer
Triple-negative breast cancer
TNBC
Endometrial carcinoma
Non-small cell lung cancer
NSCLC
SqCC
AC
ACC
Pfizer
Seattle Genetics
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2022-01-18
Enrollment: 236
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to test the safety of the medicine called Felmetatug Vedotin alone and with pembrolizumab in participants with solid tumors. It will also look at the side effects of this medicine. A side effect is anything a medicine does to the body besides treating the disease.

This study is seeking for participants who either have cancer:

* that has spread in the body near where it started (locally advanced) and cannot be removed (unresectable),
* has spread through the body (metastatic), or have some cancer left over after surgery.

This study will have five parts.

* Parts A and B of the study will find out how much Felmetatug Vedotin should be given to participants.
* Part C will use the amount found in Parts A and B to find out how safe Felmetatug Vedotin is and if it works to treat solid tumor cancers.
* Part D will find out if and how much Felmetatug Vedotin can be given with pembrolizumab.
* Part E will use the amount found in Part D to find out how safe Felmetatug Vedotin with pembrolizumab is and if it works to treat triple negative breast cancer.


Eligibility criteria: Inclusion Criteria:

For Parts A, B, and C:

* Participants must have one of the following histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumor types:

  * High-grade serous epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer
  * HER2-negative, HR positive breast cancer
  * Triple-negative breast cancer (TNBC)
  * Endometrial carcinoma
  * Non-small cell lung cancer (Squamous cell carcinoma \[SqCC\], Adenocarcinoma \[AC\])
  * Cholangiocarcinoma or gallbladder carcinoma
  * Adenoid cystic carcinoma (ACC) For Part D: Participants must have histologically or cytologically confirmed locally advanced unresectable or metastatic TNBC.

For Part E:

* Cohort E1: Participants must have histologically or cytologically confirmed locally advanced unresectable or metastatic TNBC and must have CPS≥10 by local testing
* Cohort E2: Participants must have histologically or cytologically confirmed locally advanced unresectable or metastatic TNBC and must have CPS\<10 by local testing
* Cohort E3: Participants must have triple negative breast cancer with residual disease following neoadjuvant therapy and definitive surgery

  * Parts A and B: Participants must have disease that is relapsed or refractory or be intolerant to SOC therapies, and, in the judgement of the investigator, should have no appropriate SOC therapeutic option
  * Part C: Participants must have disease that is relapsed or refractory or be intolerant to SOC therapies.
  * Part D and E1/E2: Participants must have had no prior treatment for locally advanced unresectable or metastatic TNBC
  * Part E3: Participants must have completed at least 6 cycles of neoadjuvant therapy for locally advanced unresectable or metastatic TNBC
  * Tumor tissue is required for enrollment.
  * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  * Measurable disease per RECIST version 1.1 at baseline (not applicable for E3 participants).

Exclusion Criteria:

* History of another malignancy within 3 years before the first dose of study drug. 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 corticosteroids prescribed for symptoms associated with brain metastases for at least 7 days prior to the first dose of study treatment.
* Carcinomatous meningitis
* Previous receipt of an MMAE-containing agent or an agent targeting B7-H4
* Pre-existing neuropathy ≥ Grade 2 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
* Corneal disease or injury requiring treatment or active monitoring

Primary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: Through 30 days after last study treatment, up to approximately 5 years
measure: Number of participants with laboratory abnormalities
timeFrame: Through 30-37 days after last study treatment, up to approximately 5 years
measure: Number of participants with dose limiting toxicities (DLTs)
timeFrame: Up to 28 days
measure: Number of participants with dose limiting toxicities (DLTs) and overall safety by dose level
timeFrame: Through 30-37 days after last study treatment; up to approximately 5 years
Secondary outcomes:
measure: Confirmed objective response rate (ORR) by investigator assessment
timeFrame: Up to approximately 5 years
measure: Complete response rate (CRR)
timeFrame: Up to approximately 5 years
measure: Duration of response (DOR)
timeFrame: Up to approximately 5 years
measure: Progression-free survival (PFS)
timeFrame: Up to approximately 5 years
measure: Invasive disease-free survival (iDFS)
timeFrame: Up to approximately 5 years
measure: Pharmacokinetic (PK) parameter - Area under the curve (AUC)
timeFrame: Through 30-37 days after last study treatment; up to approximately 3 years
measure: PK parameter - Maximum concentration (Cmax)
timeFrame: Through 30-37 days after last study treatment, up to approximately 3 years
measure: PK parameter - Time to maximum concentration (Tmax)
timeFrame: Through 30-37 days after last study treatment, up to approximately 3 years
measure: PK parameter - Apparent terminal half-life (t1/2)
timeFrame: Through 30-37 days after last study treatment, up to approximately 3 years
measure: PK parameter - Trough concentration (Ctrough)
timeFrame: Through 30-37 days after last study treatment, up to approximately 3 years
measure: Incidence of antidrug antibodies (ADAs)
timeFrame: Through 30-37 days after last study treatment, up to approximately 3 years
Other outcomes:
Locations:
city: Aurora
country: United States
facility: UCHealth Sue Anschutz-Rodgers Eye Center
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
state: Colorado
city: Denver
country: United States
facility: Presbyterian/St Lukes Medical Center
state: Colorado
city: Celebration
country: United States
facility: AdventHealth Celebration Infusion Center
state: Florida
city: Celebration
country: United States
facility: AdventHealth Medical Group Oncology Research at Celebration
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Orlando
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Orlando
country: United States
facility: Sarah Cannon Research Institute at Florida Cancer Specialists
state: Florida
city: Chicago
country: United States
facility: Northwestern Medical Group
state: Illinois
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Community Health Network, Inc.
state: Indiana
city: Indianapolis
country: United States
facility: Community Health Network, Inc.
state: Indiana
city: Indianapolis
country: United States
facility: Community Health Network, Inc.
state: Indiana
city: Grand Rapids
country: United States
facility: South Texas Accelerated Research Therapeutics Midwest
state: Michigan
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Nashville
country: United States
facility: Sarah Cannon Research Institute - Pharmacy
state: Tennessee
city: Houston
country: United States
facility: The University of Texas M.D. Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center Investigational Pharmacy Services
state: Texas
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics, LLC
state: Texas
city: West Valley City
country: United States
facility: South Texas Accelerated Research Therapeutics Mountain Region
state: Utah
city: West Valley City
country: United States
facility: START Mountain Region
state: Utah
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Berlin
country: Germany
facility: Hamato-Onkologische Phase 1 Unit der Charite/Charite Research Organisation
city: Milan
country: Italy
facility: Istituto Europeo di Oncologia
state: Lombardia
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: START Madrid-Hospital Universitario HM Sanchinarro
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: