A Study in Participants With Advanced Cancers Associated With Expression of DLL3 (MK-6070-001/HPN328-4001)

Clinicaltrials.gov ID: NCT04471727
db-list-check Status RECRUITING
b-loader Phase PHASE1, PHASE2
b-people Age ≥ 18 Years
b-bullseye-arrow Enrollments 232

Conditions

Small-Cell Lung Cancer, Neuroendocrine Carcinoma

Summary

This study will investigate the maximum tolerated dose, the recommended dose for expansion (RDE), safety, efficacy, and pharmacokinetics of MK-6070 alone, MK-6070 with Atezolizumab and MK-6070 with I-DXd in participants with advanced cancers associated with expression of Delta-like Canonical Notch Ligand 3 (DLL3).

Locations

11 locations Found with status Recruiting

Status

  • RECRUITING

Contact Person

Study Director

  • Medical Director

Status

  • RECRUITING

Contact Person

Study Director

  • Medical Director

Status

  • RECRUITING

Contact Person

Study Director

  • Medical Director

Status

  • RECRUITING

Contact Person

Study Director

  • Medical Director

Status

  • RECRUITING

Contact Person

Study Director

  • Medical Director

Status

  • RECRUITING

Contact Person

Study Director

  • Medical Director

Status

  • RECRUITING

Contact Person

Study Director

  • Medical Director

Status

  • RECRUITING

Contact Person

Study Director

  • Medical Director

Status

  • RECRUITING

Contact Person

Study Director

  • Medical Director

Status

  • RECRUITING

Contact Person

Study Director

  • Medical Director

Status

  • RECRUITING

Contact Person

Study Director

  • Medical Director

Eligibility Criteria

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

* Has a histologically or cytologically confirmed malignancy associated with expression of Delta-like Canonical Notch Ligand 3 (DLL3)
* Has small cell lung cancer (SCLC) which is relapsed/refractory following at least 1 prior line of systemic therapy that included platinum-based chemotherapy
* Has Neuroendocrine Prostate Cancer (NEPC; de novo or treatment-emergent) which is relapsed/refractory to standard systemic therapy
* Has high-grade neuroendocrine tumor types other than SCLC and NEPC, with at least one of the following:

* Disease that is relapsed/refractory to standard systemic therapy
* Disease for which standard therapy does not exist
* Disease for which standard therapy is not considered appropriate by the Investigator
* Must be able to provide archival tissue sample or fresh biopsy tissue sample

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

* Has untreated central nervous system (CNS) metastases
* Has a glioma or other primary CNS malignancy
* Has spinal cord compression or symptomatic/uncontrolled epidural disease
* Has a history of intracranial hemorrhage or spinal cord hemorrhage
* Has active neurologic paraneoplastic syndrome
* Has uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (e.g., biweekly or more frequently)
* Has active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis
* Is ongoing treatment with immunosuppressive medications (including, but not limited to, systemic corticosteroids [prednisone dose >10mg per day or equivalent], cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] alpha agents) within 2 weeks prior to initiation of treatment, or anticipation of need for systemic immunosuppressive medication during study treatment (except protocol-required pre-medications)
* Has a history of clinically significant cardiovascular disease such as myocardial infarction, symptomatic congestive heart failure (New York Heart Association > class II), and/or uncontrolled cardiac arrhythmia within 6 months of the first dose of study drug
* Has a history of arterial thrombosis (e.g., stroke or transient ischemic attack) within 6 months
* Has active viral hepatitis, defined as hepatitis A (hepatitis A virus immunoglobulin M [IgM] positive), hepatitis B (hepatitis B virus surface antigen [HbsAg] positive), or hepatitis C (hepatitis C virus [HCV] antibody positive, confirmed by HCV ribonucleic acid). HCV with undetectable virus after treatment are eligible. Hepatitis B virus (HBV) with undetectable viral load by quantitative polymerase chain reaction (PCR) are eligible.
* Has uncontrolled infection with Human Immunodeficiency Virus (HIV)-1 or HIV-2. Well-controlled HIV are eligible.
* Has a history of allogeneic stem cell transplant or solid-organ transplant
* Has had treatment with systemic immunostimulatory agents (including, but not limited to, interferon and IL-2) within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
* Has a history of severe anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
* Has a history of interstitial lung disease, idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT). History of radiation pneumonitis in the radiation field is permitted
* Has had treatment with other investigational drug within 3 weeks of scheduled dosing (or 5 half-lives of drug, whichever is shorter)

Study Plan

MK-6070 monotherapy dose escalation with 1 week dosing interval

EXPERIMENTAL

Participants will receive MK-6070 once weekly (Q1W) via intravenous (IV) infusion during each 21-day cycle. Dose escalation may continue until one or more RDEs are identified, participant discontinuation or the Sponsor decides to stop enrollment.

  • BIOLOGICAL:

    MK-6070

    Description:

    IV infusion

MK-6070 monotherapy dose escalation with 2 week dosing interval

EXPERIMENTAL

Participants will receive MK-6070 via IV infusion once every 2 weeks (Q2W) of a 28-day cycle. Dose escalation may continue until one or more RDEs are identified, participant discontinuation, or the Sponsor decides to stop enrollment.

  • BIOLOGICAL:

    MK-6070

    Description:

    IV infusion

MK-6070 monotherapy dose escalation with 3 week dosing interval

EXPERIMENTAL

Participants will receive MK-6070 via IV infusion once every 3 weeks (Q3W) of a 21-day cycle. Dose escalation may continue until one or more RDEs are identified, participant discontinuation, or the Sponsor decides to stop enrollment.

  • BIOLOGICAL:

    MK-6070

    Description:

    IV infusion

MK-6070 dose escalation with atezolizumab

EXPERIMENTAL

Small cell lung cancer (SCLC) participants will receive MK-6070 via IV infusion Q2W during each 28-day cycle and Atezolizumab via IV infusion every 4 weeks (Q4W) on Day 1 of each 28-day cycle. Dose escalation may continue until one or more RDEs are identified, participant discontinuation, or the Sponsor decides to stop enrollment.

  • BIOLOGICAL:

    MK-6070

    Description:

    IV infusion
  • BIOLOGICAL:

    Atezolizumab

    Description:

    IV infusion

MK-6070 dose escalation in combination with I-DXd

EXPERIMENTAL

SCLC participants will receive MK-6070 via IV infusion Q2W during each 42-day cycle and I-DXd via IV infusion Q3W on Day 1 and Day 22 of each 42-day cycle. Dose escalation may continue until one or more RDEs are identified, participant discontinuation, or the Sponsor decides to stop enrollment.

  • BIOLOGICAL:

    MK-6070

    Description:

    IV infusion
  • BIOLOGICAL:

    Ifinatamab Deruxtecan (I-DXd)

    Description:

    IV infusion

Outcome Measures

Primary Outcome Measures

Percentage of participants who experience an adverse event

Time Frame: Up to ~4 years

Percentage of participants who discontinue due to an adverse event

Time Frame: Up to ~4 years

Number of participants with dose limiting toxicity (DLT) following treatment with HPN328 as monotherapy or in combination with atezolizumab or I-DXd

Time Frame: Up to ~4 years

Maximum concentration (Cmax) of MK-6070

Time Frame: At designated time points up to ~4 years

Cmax of Atezolizumab

Time Frame: At designated time points up to ~4 years

Cmax of I-DXd

Time Frame: At designated time points up to ~4 years

Time to maximum concentration (Tmax) of MK-6070

Time Frame: At designated time points up to ~4 years

Tmax of atezolizumab

Time Frame: At designated time points up to ~4 years

Tmax of I-DXd

Time Frame: At designated time points up to ~4 years

Area under the concentration-time curve over the dosing interval t (AUCt) of MK-6070

Time Frame: At designated time points up to ~4 years

AUCt of atezolizumab

Time Frame: At designated time points up to ~4 years

AUCt of I-DXd

Time Frame: At designated time points up to ~4 years

Area under the concentration-time curve extrapolated to infinity (AUCinf) of MK-6070

Time Frame: At designated time points up to ~4 years

AUCinf of atezolizumab

Time Frame: At designated time points up to ~4 years

AUCinf of I-DXd

Time Frame: At designated time points up to ~4 years

Terminal half-life (t1/2) of MK-6070

Time Frame: At designated time points up to ~4 years

t1/2 of atezolizumab

Time Frame: At designated time points up to ~4 years

t1/2 of I-DXd

Time Frame: At designated time points up to ~4 years

Single dose clearance (CL) of MK-6070

Time Frame: At designated time points up to ~4 years

CL of atezolizumab

Time Frame: At designated time points up to ~4 years

CL of I-DXd

Time Frame: At designated time points up to ~4 years

Steady state maximum concentration (Cmax,ss) of MK-6070

Time Frame: At designated time points up to ~4 years

Cmax,ss of atezolizumab

Time Frame: At designated time points up to ~4 years

Cmax,ss of I-DXd

Time Frame: At designated time points up to ~4 years

Steady state Ctrough (Ctrough,ss) of MK-6070

Time Frame: At designated time points up to ~4 years

Ctrough,ss of atezolizumab

Time Frame: At designated time points up to ~4 years

Ctrough,ss of I-DXd

Time Frame: At designated time points up to ~4 years

Steady state time to maximum concentration (Tmax,ss) of MK-6070

Time Frame: At designated time points up to ~4 years

Tmax,ss of atezolizumab

Time Frame: At designated time points up to ~4 years

Tmax,ss of I-DXd

Time Frame: At designated time points up to ~4 years

Area under the steady state concentration-time curve over dosing interval t (AUCt,ss) of MK-6070

Time Frame: At designated time points up to ~4 years

AUCt,ss of atezolizumab

Time Frame: At designated time points up to ~4 years

AUCt,ss of I-DXd

Time Frame: At designated time points up to ~4 years

Steady state t1/2 (t1/2,ss) of MK-6070

Time Frame: At designated time points up to ~4 years

t1/2,ss of MK-6070 with atezolizumab

Time Frame: At designated time points up to ~4 years

t1/2,ss of IDXd

Time Frame: At designated time points up to ~4 years

Steady state CL (CL,ss) of MK-6070

Time Frame: At designated time points up to ~4 years

CL,ss of MK-6070 with atezolizumab

Time Frame: At designated time points up to ~4 years

CL,ss of I-DXd

Time Frame: At designated time points up to ~4 years

Steady state volume of distribution (V,ss) of MK-6070

Time Frame: At designated time points up to ~4 years

V,ss of atezolizumab

Time Frame: At designated time points up to ~4 years

V,ss of I-DXd

Time Frame: At designated time points up to ~4 years

Steady state accumulation ratio (AC) of MK-6070

Time Frame: At designated time points up to ~4 years

AC of atezolizumab

Time Frame: At designated time points up to ~4 years

AC of I-DXd

Time Frame: At designated time points up to ~4 years

Secondary Outcome Measures

Objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) (Prostate cancer clinical trials working group 3 (PCWG3) for participants with neuroendocrine prostate cancer (NEPC))

Time Frame: Up to ~4 years

Extra-cranial objective response rate (EC-ORR) based on modified RECIST v1.1

Time Frame: Up to ~4 years

Best Overall Response (BOR)

Time Frame: Up to ~4 years

Progression-free survival (PFS)

Time Frame: Up to ~4 years

Extra-cranial progression free survival (EC-PFS)

Time Frame: Up to ~4 years

Overall survival (OS)

Time Frame: Up to ~4 years

Duration of response (DOR)

Time Frame: Up to ~4 years

Duration of extra-cranial response (EC-DOR)

Time Frame: Up to ~4 years

Incidence of anti-drug antibodies (ADAs) against MK-6070

Time Frame: At designated time points up to ~4 years

Incidence of ADAs against atezolizumab (for combination-treatment patients)

Time Frame: At designated time points up to ~4 years

Incidence of ADAs against I-DXd (for combination-treatment patients)

Time Frame: At designated time points up to ~4 years

Timeline

  • Last Updated
    October 15, 2024
  • Start Date
    July 15, 2020
  • Today
    February 5, 2025
  • Completion Date ( Estimated )
    February 27, 2026

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