A Study of PF-08052666/SGN-MesoC2 in Advanced Solid Tumors

Registration Number
NCT06466187
Lead Sponsor
Seagen Inc.
Brief Summary

This clinical trial is studying advanced solid tumors. Solid tumors are cancers that start in a part of your body like your lungs or liver instead of your blood. Once tumors have grown bigger in one place but haven't spread, they're called locally advanced. If your cancer has spread to other parts of your body, it's called metastatic. When a cancer has gotte...

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
365
Inclusion Criteria
  • An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
  • Participants must have histologically- or cytologically-confirmed metastatic or locally advanced unresectable ovarian cancer, non-small cell lung cancer (NSCLC), pancreatic adenocarcinoma, endometrial cancer (EC), colorectal cancer (CRC), mesothelioma.
  • Must have at least one measurable lesion at baseline based on RECIST v1.1.
  • Archival tumor tissue is required, or, if unavailable, a fresh tumor biopsy (if it is safe and feasible) during the screening period.
  • Participants weighing ≥40 kg
  • Additional inclusion criterion for platinum resistant ovarian cancer (PROC) participants: Histologically or cytologically documented invasive epithelial ovarian, primary peritoneal, or fallopian tube cancer (tumors with pseudomyxomatous or mucinous histology are excluded) or advanced predominantly epithelioid peritoneal, must have relapsed or progressed following local standard therapies or for which no standard therapy is available.
  • Platinum prior exposure unless it is contraindicated or not available.
  • Participants with known FRa high expression, must have progressed after mirvetuximab soravtansine or other FRa-directed therapy) unless contraindicated or not available. Participants whose cancer is associated with homologous recombination deficiency (HRD)-positive status must have been exposed to PARP inhibitors, unless contraindicated or not available.
  • Additional inclusion criterion for pancreatic ductal adenocarcinoma (PDAC) participants (Part A only): Histologically or cytologically documented, locally advanced unresectable or metastatic pancreatic adenocarcinoma, including recurrence of previously resected disease.
  • Participant must have progressed after standard cytotoxic therapies, or for which no standard therapy is available. Participants must have received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, gemcitabine and nab-paclitaxel combination or gemcitabine-based chemotherapy.
  • Additional inclusion criterion for NSCLC participants (Part A only): Histologically or cytologically confirmed advanced and/or metastatic NSCLC, must have progressed after standard therapies, or for which no standard therapy is available.
  • Participants do not need to have expression of MSLN in tumor to be selected for Part C enrollment unless retrospective analysis of the immunohistochemistry (IHC) data in dose escalation suggests it as a requirement.
  • a. If participants have a specific mutation for which standard therapy is available (eg, ALK, ROS1, MET, NTRK, BRAF V600E, EGFR Exon 20 ins, RET, KRAS G12C, HER2), they must have documented progression after treatment with appropriate tyrosine kinase inhibitor or other agent and have documented progression after platinum doublet chemotherapy treatment, unless not tolerated, contraindicated, or not available.
  • b. If participants do not have a specific mutation for which standard therapy is available, they must have documented progression after treatment with a check point inhibitor and platinum based chemotherapy, unless not tolerated, contraindicated, or not available.
  • Additional inclusion criterion for CRC participants (Part A only): Histologically confirmed metastatic or locally advanced colorectal adenocarcinoma.
  • Participant must have progressed after standard therapy, or for which no standard therapy is available. Participants must have received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, unless not tolerated, contraindicated, or not available.
  • Participants with microsatellite instability (MSI)-H/mismatch repair deficient (dMMR) tumors must have received treatment with a PD-1 mAb, unless not tolerated or available. If participants have an BRAF mutation or other mutations, they must have documented progression after treated with appropriate therapies (eg, encorafenib + cetuximab), unless not tolerated or available. Particpants with HER2 positive tumors, must have received treatment with HER2-directed therapies (eg, tucatinib + trastuzumab), unless not tolerated or available.
  • Participants do not need to have expression of MSLN in tumor to be selected for Part C enrollment unless retrospective analysis of the IHC data in dose escalation suggests it as a requirement.
  • Additional inclusion criteria for EC participants (Part A only): Participant must have received at least 1 line of platinum-based chemotherapy.
  • Participant must have received up to 2 lines of systemic therapy in metastatic setting.
  • If appropriate by biomarker status (including but not limited to microsatellite instability [MSI] and dMMR status) and available per local SOC, must have received a prior PD-1 inhibitor and/or the combination of pembrolizumab and lenvatinib, unless not tolerated.
  • Additional inclusion criteria for mesothelioma participants (Part A only): Histologically or cytologically confirmed advanced and/or metastatic mesothelioma, must have progressed after standard therapies, or for which no standard therapy is available.
  • Additional inclusion criteria for all tumor types (Parts B and C only): Participants must have histologically- or cytologically-confirmed metastatic or locally advanced unresectable ovarian cancer, non-small cell lung cancer (NSCLC), pancreatic adenocarcinoma, endometrial cancer (EC), colorectal cancer (CRC), or mesothelioma.
  • Participants must not have received more than 2 lines of cytotoxic systemic therapy in metastatic setting.
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Exclusion Criteria
  • Participants previously received or is currently receiving the following anticancer medications or investigational drugs will be excluded:

    • Any systemic anticancer therapy or focal radiotherapy within 4 weeks prior to first dose of PF-08052666or within 2 weeks prior to the first dose of PF-08052666if the underlying disease has progressed on treatment.
    • For Part C, prior anti-Mesothelin (MSLN) antibody (mAb or BsAb), MSLN- directed ADC.
  • Major surgery (excluding placement of vascular access) within 4 weeks, or minor surgery within 7 days, prior to first dose of study intervention.

Participants must have recovered adequately from the toxicity or complications from the surgery prior to starting PF-08052666. Participants who have planned major surgery during the treatment period must be excluded from the study.

  • 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.
  • Known to be positive for human immunodeficiency virus (HIV). Participants with severe or uncontrolled systemic diseases, including uncontrolled hypertension, uncontrolled diabetes mellitus, or active bleeding diatheses.
  • Participants with medical history of clinically significant lung diseases (eg, interstitial pneumonia, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis) or who are suspected to have these diseases by imaging at screening period.
  • Previously untreated brain metastases. Participants who have received radiation or surgery for brain metastases are eligible if therapy was completed at least 4 weeks prior to initiation of study treatment, there is no evidence of central nervous system (CNS) disease progression, and there is no requirement for chronic corticosteroid therapy. Leptomeningeal metastases or spinal cord compression due to disease.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
PF-08052666PF-08052666PF-08052666 monotherapy
Primary Outcome Measures
NameTimeMethod
Number of participants with adverse events (AEs)Through 30-37 days after the last dose of study treatment, 48 Months

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

Number of participants with dose modificationsUp to 4 months

Frequency of dose modifications (eg, dose delay, treatment interruptions, dose reductions and treatment discontinuations) due to AEs

Number of participants with laboratory abnormalitiesThrough 30-37 days after the last dose of study treatment, 48 Months
Number of participants with dose-limiting toxicities (DLTs)Cycle 1 (21 days)

Incidence of dose-limiting toxicities (DLTs)

Secondary Outcome Measures
NameTimeMethod
Disease control rate (DCR)Approximately 1 year 4 months

DCR is defined as the proportion of participants with best response of CR, PR or stable disease (SD) according to RECIST v1.1.

Pharmacokinetic (PK) parameter - Area under the serum concentration (AUC)Cycles 1, 2, and 3 (each cycle is up to 21 days)
Objective response rate (ORR)Approximately 1 year 4 months

ORR is defined as the proportion of participants in the relevant analysis set with best response of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Best responseApproximately 1 year 4 months

The best timepoint response achieved for the subject during the protocol specified period according to RECIST V1.1.

Overall survival (OS)Approximately 1 year 4 months

Overall survival (OS) defined as the time from first dosing to death.

Pharmacokinetic (PK) parameter - Maximum serum concentration (Cmax)Cycles 1, 2, and 3 (each cycle is up to 21 days)
Duration of response (DOR)Approximately 1 year 4 months

DOR is defined as the time interval from first occurrence of documented objective response to the time of progressive disease (PD) according to RECIST v1.1 or death from any cause, whichever comes first.

Pharmacokinetic (PK) parameter - Time to reach maximum serum concentration (Tmax)Cycles 1, 2, and 3 (each cycle is up to 21 days)
Progression-free survival (PFS)Approximately 1 year 4 months

PFS is defined as the time from first dosing to the first occurrence of PD according to RECIST v1.1 or death from any cause, whichever comes first.

Pharmacokinetic (PK) parameter - Half-lifeCycles 1, 2, and 3 (each cycle is up to 21 days)
Number of participants with antidrug antibodiesCycles 1, 2, and 3 (each cycle is up to 21 days)

Trial Locations

Locations (3)

SCRI Oncology Partners

🇺🇸

Nashville, Tennessee, United States

South Texas Accelerated Research Therapeutics

🇺🇸

San Antonio, Texas, United States

START Mountain Region

🇺🇸

West Valley City, Utah, United States

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