Clinical trial NCT06780137: A Study to Evaluate the Safety and Efficacy of Gocatamig (MK-6070) and Ifinatamab Deruxtecan (I-DXd) in Participants With Relapsed/Refractory Extensive-Stage Small Cell Lung Cancer (MK-6070-002)
Official title: A Phase 1b/2 Open-Label Clinical Study to Evaluate the Safety and Efficacy of MK-6070 and Ifinatamab Deruxtecan (I-DXd) in Participants With Relapsed/Refractory Extensive-Stage Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Small Cell Lung Cancer
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo
First posted: 2025-01-17
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part 1 consists of four arms (gocatamig and I-DXd Q3W, gocatamig Q2W and I-DXd Q3W, I-DXd monotherapy Q2W, and gocatamig and I-DXd Q2W). Participants will be randomized to one of the four arms using an interactive response technology (IRT) system. Part 2 consists of a single arm (gocatamig Monotherapy) and is only open to Japanese participants.
Primary purpose: TREATMENT

Brief summary: Researchers are looking for new ways to treat people with extensive-stage small cell lung cancer (SCLC) that has relapsed or is refractory. Gocatamig is a new type of immunotherapy that uses a person's immune system to find and destroy cancer cells. Ifinatamab deruxtecan (also known as I-DXd) is a drug which binds to a specific target on cancer cells and delivers treatment to destroy those cells. Researchers want to know if giving gocatamig and/or I-DXd can treat SCLC that did not respond or stopped responding to a prior treatment.

The goals of this study are to learn:

* If gocatamig and I-DXd are safe and well tolerated
* If people who receive gocatamig and I-DXd have their SCLC get smaller or go away

Detailed description: This study will consist of two parts. Part 1 will assess the safety, tolerability, and efficacy of gocatamig and I-DXd at dosing intervals of once every 2 weeks (Q2W) and/or once every 3 weeks (Q3W) at doses determined in study MK-6070-001 (NCT: NCT04471727). Part 2 will assess the safety and tolerability of gocatamig in Japanese participants.

Eligibility criteria: Inclusion Criteria:

* Has histologically or cytologically confirmed SCLC that is extensive stage (defined as Stage IV (T any, N any, M1a/b/c) following at least 1 prior line of systemic therapy that included platinum-based chemotherapy
* Must be able to provide archival tissue sample or fresh biopsy tissue sample
* Human immunodeficiency virus (HIV) infected participants must have well controlled HIV on antiretroviral therapy (ART)

Exclusion Criteria:

* Pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedure
* History of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD, and or suspected ILD/pneumonitis
* Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
* History of clinically significant intracranial bleeding or spinal cord bleeding
* Active neurologic paraneoplastic syndrome
* Active or history of immune deficiency with the exception of HIV-infected participants with well controlled HIV on ART
* History within 6 months before the first dose of study intervention of coronary/peripheral artery bypass graft and/or any coronary/peripheral angioplasty or clinically significant cardiovascular disease such as myocardial infarction, symptomatic congestive heart failure (CHF) (New York Heart Association \> class II), and/or uncontrolled cardiac arrhythmia
* Has other uncontrolled or significant protocol-specified cardiovascular disease
* History of arterial thrombosis (eg, stroke or transient ischemic attack) within 6 months before the first dose of study intervention
* Chronic liver disease, including liver cirrhosis of Child-Pugh class B or C
* Active clinically significant infection requiring systemic therapy
* History of allogeneic tissue/solid organ transplant
* History of leptomeningeal disease
* Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
* Ongoing treatment with immunosuppressive medications, with protocol-specified exceptions
* Known additional malignancy that is progressing or has required active treatment within the past 3 years
* Untreated or symptomatic brain metastases
* Active viral hepatitis, defined as hepatitis A (hepatitis A virus immunoglobulin M \[IgM\] positive in the setting of associated signs/symptoms), hepatitis B (hepatitis B virus surface antigen \[HbsAg\] positive and/or detectable hepatitis B virus (HBV) deoxyribonucleic acid \[DNA\]), or hepatitis C (hepatitis C virus \[HCV\] antibody positive and detectable HCV ribonucleic acid). Participants with HBV with undetectable viral load after treatment are eligible. Participants with HCV with undetectable virus after treatment are eligible.
* Part 1 only: Radiation therapy to the lung \>30 Gy within 6 months before the start of study intervention
* Part 1 only: Abdominal radiation within 4 weeks before start of study intervention
* Part 1 only: Other anticancer therapy, including cytotoxic agents, targeted agents, immunotherapies, antibody, retinoid, transplant, or anticancer hormonal treatment (except luteinizing hormone-releasing hormone \[LHRH\]) within 2 weeks before start of study intervention
* Part 1 only: Antibody-based cancer therapy within 3 weeks before start of study intervention
* Part 1 only: Chloroquine/hydroxychloroquine within 2 weeks before start of study intervention
* Part 1 only: Clinically significant corneal disease

Primary outcomes:
measure: Number of Participants Who Experience an Adverse Event (AE)
timeFrame: Up to approximately 44 months
measure: Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs)
timeFrame: Up to approximately 3 weeks
measure: Number of Participants Who Discontinue Study Intervention Due to an AE
timeFrame: Up to approximately 44 months
measure: Part 1: Objective Response Rate (ORR)
timeFrame: Up to approximately 44 months
Secondary outcomes:
measure: Part 1: Duration of Response (DOR)
timeFrame: Up to approximately 44 months
measure: Part 1: Progression-Free Survival (PFS)
timeFrame: Up to approximately 44 months
measure: Maximum Concentration (Cmax) of gocatamig
timeFrame: At designated timepoints (up to approximately 44 months)
measure: Cmax of ifinatamab deruxtecan (I-DXd)
timeFrame: At designated timepoints (up to approximately 44 months)
measure: Cmax of Anti-B7-H3 Antibody
timeFrame: At designated timepoints (up to approximately 44 months)
measure: Cmax of Deruxtecan (DXd)
timeFrame: At designated timepoints (up to approximately 44 months)
measure: Time to maximum concentration (Tmax) of gocatamig
timeFrame: At designated timepoints (up to approximately 44 months)
measure: Tmax of I-DXd
timeFrame: At designated timepoints (up to approximately 44 months)
measure: Tmax of Anti-B7-H3 Antibody
timeFrame: At designated timepoints (up to approximately 44 months)
measure: Tmax of DXd
timeFrame: At designated timepoints (up to approximately 44 months)
measure: Area Under the Concentration-Time Curve Over the Dosing Interval t (AUCt) of gocatamig
timeFrame: At designated timepoints (up to approximately 44 months)
measure: AUCt of I-DXd
timeFrame: At designated timepoints (up to approximately 44 months)
measure: AUCt of Anti-B7-H3 Antibody
timeFrame: At designated timepoints (up to approximately 44 months)
measure: AUCt of DXd
timeFrame: At designated timepoints (up to approximately 44 months)
measure: Terminal Half-Life (t1/2) of gocatamig
timeFrame: At designated timepoints (up to approximately 44 months)
measure: t1/2 of I-DXd
timeFrame: At designated timepoints (up to approximately 44 months)
measure: t1/2 of Anti-B7-H3 Antibody
timeFrame: At designated timepoints (up to approximately 44 months)
measure: t1/2 of DXd
timeFrame: At designated timepoints (up to approximately 44 months)
measure: Steady State Maximum Concentration (Cmax,ss) of gocatamig
timeFrame: At designated timepoints (up to approximately 44 months)
measure: Cmax,ss of I-DXd
timeFrame: At designated timepoints (up to approximately 44 months)
measure: Cmax,ss of Anti-B7-H3 Antibody
timeFrame: At designated timepoints (up to approximately 44 months)
measure: Cmax,ss of DXd
timeFrame: At designated timepoints (up to approximately 44 months)
measure: Steady State Ctrough (Ctrough,ss) of gocatamig
timeFrame: At designated timepoints (up to approximately 44 months)
measure: Ctrough,ss of I-DXd
timeFrame: At designated timepoints (up to approximately 44 months)
measure: Ctrough,ss of Anti-B7-H3 Antibody
timeFrame: At designated timepoints (up to approximately 44 months)
measure: Ctrough,ss of DXd
timeFrame: At designated timepoints (up to approximately 44 months)
measure: Steady State Time to Maximum Concentration (Tmax,ss) of gocatamig
timeFrame: At designated timepoints (up to approximately 44 months)
measure: Tmax,ss of I-DXd
timeFrame: At designated timepoints (up to approximately 44 months)
measure: Tmax,ss of Anti-B7-H3 Antibody
timeFrame: At designated timepoints (up to approximately 44 months)
measure: Tmax,ss of DXd
timeFrame: At designated timepoints (up to approximately 44 months)
measure: Area Under the Steady State Concentration-Time Curve Over Dosing Interval t (AUCt,ss) of gocatamig
timeFrame: At designated timepoints (up to approximately 44 months)
measure: AUCt,ss of I-DXd
timeFrame: At designated timepoints (up to approximately 44 months)
measure: AUCt,ss of Anti-B7-H3 Antibody
timeFrame: At designated timepoints (up to approximately 44 months)
measure: AUCt,ss of DXd
timeFrame: At designated timepoints (up to approximately 44 months)
measure: Steady state t1/2 (t1/2,ss) of gocatamig
timeFrame: At designated timepoints (up to approximately 44 months)
measure: t1/2,ss of I-DXd
timeFrame: At designated timepoints (up to approximately 44 months)
measure: t1/2,ss of Anti-B7-H3 Antibody
timeFrame: At designated timepoints (up to approximately 44 months)
measure: t1/2,ss of DXd
timeFrame: At designated timepoints (up to approximately 44 months)
measure: Accumulation Ratio (AC) of gocatamig
timeFrame: At designated timepoints (up to approximately 44 months)
measure: AC of I-DXd
timeFrame: At designated timepoints (up to approximately 44 months)
measure: AC of Anti-B7-H3 Antibody
timeFrame: At designated timepoints (up to approximately 44 months)
measure: AC of DXd
timeFrame: At designated timepoints (up to approximately 44 months)
measure: Incidence of Anti-Drug Antibodies (ADAs) Against gocatamig
timeFrame: At designated timepoints (up to approximately 44 months)
measure: Incidence of Anti-Drug Antibodies (ADAs) Against I-DXd
timeFrame: At designated timepoints (up to approximately 44 months)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Farber Cancer Institute ( Site 1105)
state: Massachusetts
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center ( Site 1103)
state: New Jersey
city: Nashville
country: United States
facility: Sarah Cannon Research Institute ( Site 7001)
state: Tennessee
city: Santiago.
country: Chile
facility: FALP ( Site 2100)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Bradfordhill ( Site 2101)
state: Region M. De Santiago
city: Haifa
country: Israel
facility: Rambam Health Care Campus ( Site 3202)
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center ( Site 3200)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center ( Site 3201)
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 5100)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center ( Site 5101)
city: L Eixample
country: Spain
facility: HOSPITAL CLÍNIC DE BARCELONA ( Site 3310)
state: Barcelona
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos... ( Site 3316)
state: Madrid, Comunidad De
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron ( Site 3311)
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria ( Site 3312)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: