Clinical trial NCT06120504: A Safety Study of PF-08046045/SGN-35T in Adults With Advanced Cancers
Official title: An Open-label Phase 1 Study to Evaluate the Safety of PF-08046045/SGN-35T in Adults With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Lymphoma, T-Cell, Cutaneous
Hodgkin Disease
Lymphoma, T-Cell, Peripheral
Lymphoma, Large-Cell, Anaplastic
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Non-Hodgkin
Keywords: cHL
ALCL
PCL
PTCL
DLBCL
CTCL
Non-Hodgkin Lymphoma
Seattle Genetics
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2023-11-07
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This clinical trial is studying lymphoma. Lymphoma is a cancer that starts in the blood cells that fight infections. There are several types of lymphoma. This study will enroll people who have lymphoma, such as classical Hodgkin lymphoma, peripheral T-cell lymphoma including systemic anaplastic large cell lymphoma, diffuse large B-cell lymphoma, or some types of primary cutaneous lymphoma.

This clinical trial uses a drug called PF-08046045/SGN-35T. The study drug is in testing and has not been approved for sale. This is the first time PF-08046045 will be used in people. The study drug will be given as an infusion through a vein.

This study will test the safety of PF-08046045 in participants with lymphoma. It will also study the side effects of this drug. A side effect is anything a drug does to the body besides treating the disease.

This study will have three parts. Parts A and B of the study will find out the best dose and dosing schedule for PF-08046045. Part C will use the dose found in parts A and B to find out how safe PF-08046045 is and if it works to treat select lymphomas.

Detailed description: This is a phase 1, open-label, multicenter study designed to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of PF-08046045/SGN-35T in adults with select relapsed/refractory lymphomas. PF-08046045 is a CD30-directed antibody-drug conjugate and will be studied in patients with lymphomas expressing CD30.

Eligibility criteria: Inclusion Criteria:

* Disease indication

  * For dose escalation and dose optimization (Part A and Part B):

    * Participants with a histologically confirmed lymphoid neoplasm (including relapsed/refractory \[R/R\] classical Hodgkin lymphoma \[cHL\], R/R peripheral T-cell lymphoma \[PTCL\], R/R systemic anaplastic large cell lymphoma \[sALCL\] , R/R mature B-cell neoplasms, and select R/R primary cutaneous lymphomas \[PCLs\]) who in the judgment of the investigator have no appropriate standard therapy available at the time of enrollment and are a candidate for PF-08046045 treatment.
    * Participants must have a detectable CD30 expression level (≥1%) in tumor tissue (except cHL and ALCL where CD30 is universally expressed).
  * For dose expansion (Part C)

    * Participants are eligible irrespective of CD30 expression on tumor tissue.
    * Participants with cHL: Participants with R/R cHL who have received at least 3 prior systemic therapies (autologous stem cell transplant \[ASCT\] and the associated high dose chemotherapy prior to ASCT are considered to be 1 prior line, along with post-transplant consolidation if progression has not occurred between transplant and start of consolidation) and meet all of the following additional criteria:

      * Participants who have not received ASCT must have refused or been deemed ineligible.
      * Participants must have received or been ineligible to receive an anti-PD-1 agent.
    * Participants with PTCL:

      * Participants with R/R PTCL (excluding R/R sALCL) who have received at least 2 prior systemic therapies or received at least 1 prior systemic therapy and there is no other available treatment that is considered appropriate by the investigator.
      * Participants with R/R sALCL must have ALK status documented and must meet one of the following criteria:

        * Disease recurrence or progression following at least 2 prior systemic therapies where 1 regimen included brentuximab vedotin, or
        * Disease recurrence or progression following only 1 prior line of therapy which included brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone
* An Eastern Cooperative Oncology Group (ECOG) Performance Status score ≤1.
* Fluorodeoxyglucose positron emission tomography (FDG PET) avid and bidimensional measurable disease as documented by radiographic technique (spiral CT preferred) per Lugano criteria at baseline (Cheson 2014) (not applicable for subjects with PCL).

Exclusion Criteria:

* Participants who have received more than 2 prior brentuximab vedotin-based lines of therapy.
* History of another malignancy within 3 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death.
* Active cerebral/meningeal disease related to the underlying malignancy.
* Received previous ASCT infusion \<12 weeks prior to first PF-08046045 dose.
* Participants with previous allogeneic stem cell transplant (SCT) if they meet any of the following criteria:

  * \<100 days from allogeneic SCT. Participants ≥100 days from allogeneic SCT who are stable without immunosuppressive therapy for at least 12 weeks are permitted.
  * Active acute or chronic graft versus host disease or receiving immunosuppressive therapy as treatment for or prophylaxis against graft versus host disease.
* Participants with previous allogeneic SCT and participants considered at high risk for CMV reactivation (eg, recent prior CAR-T or bispecific antibody therapy) if they meet the following criteria: Cytomegalovirus (CMV) PCR ≥500 IU/mL, OR rising DNA levels \>5-times baseline within 1 month, OR detectable CMV PCR receiving pre-emptive therapy; prior PCR positivity that was successfully treated is acceptable provided the baseline PCR result is negative prior to the first dose of study intervention.
* Grade 2 or higher pulmonary disease unrelated to underlying malignancy, or history of Grade 2 or higher drug-induced interstitial lung disease (ILD) or immune checkpoint inhibitor (ICI)-related ILD.
* Clinically significant lung disease requiring systemic corticosteroid treatment within 6 months prior to enrollment or who are suspected to have such diseases via radiographic imaging and/or functional tests conducted during the screening period.

Primary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: Through 30-37 days after last study treatment, approximately 1 year
measure: Number of participants with laboratory abnormalities
timeFrame: Through 30-37 days after last study treatment, approximately 1 year
measure: Number of participants with dose modifications due to AEs
timeFrame: Up to approximately 1 year
measure: Number of participants with dose-limiting toxicities (DLTs)
timeFrame: Up to 21 days
measure: Number of participants with DLTs by dose level
timeFrame: Up to 21 days
Secondary outcomes:
measure: Pharmacokinetic (PK) parameter - Area under the concentration-time curve (AUC)
timeFrame: Through 30-37 days after last study treatment, approximately 1 year
measure: PK parameter - Maximum concentration (Cmax)
timeFrame: Through 30-37 days after last study treatment, approximately 1 year
measure: PK parameter - Time to Cmax (Tmax)
timeFrame: Through 30-37 days after last study treatment, approximately 1 year
measure: Number of participants with antidrug antibodies (ADA)
timeFrame: Through 30-37 days after last study treatment, approximately 1 year
measure: Objective response rate (ORR) as assessed by the investigator
timeFrame: Up to approximately 1 year
measure: Complete response (CR) rate as assessed by the investigator
timeFrame: Up to approximately 1 year
measure: Duration of response (DOR)
timeFrame: Up to approximately 1 year
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas For Medical Sciences
state: Arkansas
city: Palo Alto
country: United States
facility: Stanford Cancer Center / Blood and Marrow Transplant Program
state: California
city: Coral Gables
country: United States
facility: University of Miami Hospital and Clinics - Lennar
state: Florida
city: Miami
country: United States
facility: University of Miami Hospital And Clinics
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
city: Iowa City
country: United States
facility: University Of Iowa Hospitals And Clinics
state: Iowa
city: Basking Ridge
country: United States
facility: MSK Basking Ridge
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Middletown
country: United States
facility: MSK Monmouth.
state: New Jersey
city: Montvale
country: United States
facility: MSK Bergen.
state: New Jersey
city: Paramus
country: United States
facility: Hackensack University Medical Center (From Road)
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Commack
country: United States
facility: MSK Commack.
state: New York
city: Harrison
country: United States
facility: MSK Westchester.
state: New York
city: Long Island City
country: United States
facility: Memorial Sloan Kettering Cancer Center-Investigational Drug Service Pharmacy
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center - David H. Koch Center for Cancer Care (74th Street).
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center-Main Campus
state: New York
city: Uniondale
country: United States
facility: MSK Nassau.
state: New York
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Toronto
country: Canada
facility: University Health Network, Princess Margaret hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University Department of Oncology/McGill University Health Centre
state: Quebec
city: Copenhagen
country: Denmark
facility: Region Hovedstadens Apotek Serviceproduktion
city: Copenhagen
country: Denmark
facility: Rigshospitalet University Hospital of Copenhagen
city: Alessandria
country: Italy
facility: SC Farmacia Ospedaliera Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo
state: Other
city: Alessandria
country: Italy
facility: SC Medicina Nucleare Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo
state: Other
city: Alessandria
country: Italy
facility: SC Radiologia Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo
state: Other
city: Alessandria
country: Italy
facility: SCDU Ematologia Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo
state: Piedmont
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital, Pharmacy Stores
state: Surrey
city: London
country: United Kingdom
facility: University College London Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: London
country: United Kingdom
facility: NIHR UCLH Clinical Research Facility
city: Oxford
country: United Kingdom
facility: Cancer and Haematology Centre
city: Oxford
country: United Kingdom
facility: Clinical Trials Aseptic Unit (CTASU) Churchill Hospital
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: