Clinical trial NCT05983133: A Study of PF-08046052/SGN-EGFRd2 in Advanced Solid Tumors
Official title: A Phase 1 Study of PF-08046052/SGN-EGFRd2 in Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Colorectal Neoplasms
Carcinoma, Non-Small-Cell Lung
Squamous Cell Carcinoma of the Head and Neck
Pancreatic Ductal Adenocarcinoma
Keywords: CRC
Colon Cancer
Rectal Cancer
NSCLC
HNSCC
PDAC
Seattle Genetics
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2023-08-09
Enrollment: 290
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 study will test the safety of a drug called PF-08046052/SGN-EGFRd2 in participants with advanced solid tumors. 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.

Participants will have cancer that cannot be removed (unresectable) or has spread through the body (metastatic).

This study will have three parts. Parts A and B of the study will find out how much PF-08046052/SGN-EGFRd2 should be given to participants. Part C will use the dose found in parts A and B to find out how safe PF-08046052/SGN-EGFRd2 is and if it works to treat solid tumor cancers.


Eligibility criteria: Inclusion Criteria:

* Tumor types:

  * For Part A: Participants must have disease that is relapsed, refractory, or be intolerant to standard of care therapies, and in the judgement of the investigator must have no appropriate standard therapy available at the time of enrollment. Participants must have histologically- or cytologically confirmed metastatic or unresectable solid malignancy from one of the following tumor types:

    * Colorectal cancer (CRC)
    * Non-small cell lung cancer (NSCLC)
    * Head and neck squamous cell cancer (HNSCC)-non-nasopharyngeal subtype ONLY; nasopharyngeal subtype is not eligible.
  * For Part B: Participants must have disease that is relapsed, refractory, or be intolerant to standard of care therapies, and in the judgement of the investigator must have no appropriate standard therapy available at the time of enrollment.

    * The tumor type(s) to be enrolled in dose optimization will be identified by the sponsor from among those specified in Part A.
  * For Part C: Participants must have disease that is relapsed or refractory or be intolerant to standard of care therapies as specified below, unless contraindicated:

    * CRC

      * Participants must have unresectable locally advanced or metastatic CRC.
      * Prior therapy: Participants must have received prior fluoropyrimidine, oxaliplatin and irinotecan. Participants with defective mismatch repair and microsatellite instability high (dMMR/MSI-H) should have received prior treatment with pembrolizumab, a nivolumab-containing regimen, or other available anti-PD-1 (programmed cell death protein 1) or anti PD L1 (programmed cell death 1 ligand) agents.
    * NSCLC

      * Participants must have unresectable locally advanced or metastatic NSCLC.
      * Prior therapy: Participants must have received platinum-based therapy and at least 1 PD-1/PD-L1 inhibitor. These agents may have been administered either as single agents or in combination. Participants with an activating mutation or rearrangement (eg, EGFR, anaplastic lymphoma kinase \[ALK\], etc.) must have received available targeted agents if eligible by biomarker status and local standard of care.
    * HNSCC

      * Participants must have unresectable locally advanced or metastatic HNSCC - non-nasopharyngeal subtype ONLY; nasopharyngeal subtype is not eligible.
      * Prior therapy: Participants must have received platinum-based therapy and a PD-1/PD-L1 inhibitor, if eligible by biomarker status and local standard of care. These agents may have been administered either as single agents or in combination.
    * Pancreatic ductal adenocarcinoma (PDAC)

      * Participants must have unresectable locally advanced or metastatic PDAC.
      * Prior therapy: Participants must have received gemcitabine- or FOLFIRINOX-based therapy.
* Participants should provide archival tumor tissue if available and also agree to biopsies, if medically feasible
* An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
* Measurable disease at baseline per RECIST 1.1 criteria.

Exclusion Criteria:

* History of another malignancy within 3 years before the first dose of study treatment, 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 or leptomeningeal disease. Participants with previously treated brain metastases may participate provided they are

  * clinically stable for at least 4 weeks prior to study entry after brain metastases treatment,
  * they 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 the first dose of study drug.
* Treatment with an aminobisphosphonate IV (eg ibandronate, pamidronate, zoledronate, etc.) within 4 weeks of the first dose of study treatment.
* Participants with history of thromboembolic phenomena within 6 months prior to the first dose of study intervention, or with contraindication to thromboembolism prophylaxis (if clinically indicated) for a previous history of thrombus.

Primary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: Through 90 days after last study treatment, up to approximately 1 year
measure: Number of participants with laboratory abnormalities
timeFrame: Through 30-37 days after last study treatment, up to approximately 1 year
measure: Number of participants with dose limiting toxicities (DLTs)
timeFrame: Up to 35 days
measure: Number of participants with DLTs by dose level
timeFrame: Up to 35 days
Secondary outcomes:
measure: Number of participants with antidrug antibodies (ADAs)
timeFrame: Through 30-37 days after last study treatment, up to approximately 1 year
measure: Pharmacokinetic (PK) parameter - Area under the curve (AUC)
timeFrame: Through 30-37 days after last study treatment, up to approximately 1 year
measure: PK parameter - Maximum concentration (Cmax)
timeFrame: Through 30-37 days after last study treatment, up to approximately 1 year
measure: PK parameter - Time to maximum concentration (Tmax)
timeFrame: Through 30-37 days after last study treatment, up to approximately 1 year
measure: PK parameter - Apparent terminal half-life (t1/2)
timeFrame: Through 30-37 days after last study treatment, up to approximately 1 year
measure: PK parameter - Trough concentration (Ctrough)
timeFrame: Through 30-37 days after last study treatment, up to approximately 1 year
measure: Objective response rate (ORR)
timeFrame: Up to approximately 2 years
measure: Duration of response (DOR)
timeFrame: Up to approximately 2 years
measure: Progression-free survival (PFS)
timeFrame: Up to approximately 2 years
measure: Overall survival (OS)
timeFrame: Up to approximately 3 years
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: UCLA Department of Medicine - Hematology & Oncology
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center McKinley Hospital
state: Florida
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center / Wake Forest University
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Portland
country: United States
facility: Providence Cancer Institute Franz Clinic
state: Oregon
city: Houston
country: United States
facility: MD Anderson Cancer Center - University of Texas
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute, University Of Utah
state: Utah
city: London
country: United Kingdom
facility: University College London Hospital, NIHR UCLH Clinical Research Facility
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: