Clinical trial NCT06049212: Sacituzumab Tirumotecan (MK-2870) as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors (MK-2870-008)
Official title: Phase 1 Trial of MK-2870 as Monotherapy and in Combination With Pembrolizumab ± Chemotherapy in Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Non-small Cell Lung Cancer
Solid Tumors
Programmed Cell Death-1 (PD1, PD-1)
Programmed Cell Death 1 Ligand 1(PDL1, PD-L1)
Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2023-09-22
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a phase 1 trial of the safety, tolerability, and pharmacokinetics (PK) of sacituzumab tirumotecan monotherapy, and of sacituzumab tirumotecan in combination with pembrolizumab (MK-3475) or pembrolizumab + carboplatin, in Japanese participants with advanced solid tumors or treatment-naïve advanced or metastatic non-small cell lung cancer (NSCLC).

Per protocol amendment 04, Arm 3: Pembrolizumab/Carboplatin + sacituzumab tirumotecan Combination Therapy was discontinued, and subsequently all Arm 3 procedures, recruitment, and descriptions were removed.


Eligibility criteria: Inclusion Criteria:

* Arm 1: Histologically or cytologically confirmed advanced/metastatic solid tumor by pathology report and have received, or been intolerant to, all treatment known to confer clinical benefit.
* Arm 2: Have a histologically or cytologically confirmed diagnosis of advanced or metastatic NSCLC (Stage IIIB or IIIC disease and not candidates for surgical resection or definitive chemoradiation, or Stage IV NSCLC, AJCC Staging Manual, version 8).
* Arm 2: Confirmation that EGFR-, ALK-, or ROS1-directed therapy is not indicated as primary therapy
* Arm 2: Has tumor tissue that demonstrates PD-L1 TPS ≥ 50% as determined by PD-L1 IHC 22C3 pharmDx assay by local laboratory
* If capable of producing sperm, the participant agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention (100 days for sacituzumab tirumotecan and 90 days for carboplatin \[no restriction for pembrolizumab\]) AND agrees to refrain from donating sperm AND is either abstinent and agrees to remain abstinent or uses highly effective contraception
* For females (assigned at birth), is not pregnant or breastfeeding and ≥1 of the following applies: is not a participant of childbearing potential (POCBP) OR is a POCBP and uses highly effective contraception
* Arm 1: Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline
* Measurable disease by RECIST 1.1 as assessed by the local site investigator/radiology
* Archival tumor tissue sample or newly obtained core or incisional biopsy of a tumor lesion not previously irradiated has been provided
* Have a life expectancy of at least 3 months
* Have an ECOG performance status of 0 or 1 within 3 days before the start of study intervention

Exclusion Criteria:

* Has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible
* Has Grade ≥2 peripheral neuropathy
* Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to \>480 ms, and/or other serious cardiovascular and cerebrovascular diseases within the 6 months preceding study intervention
* Received prior treatment with a TROP2-targeted ADC
* Received prior treatment with a topoisomerase I-containing ADC
* Arm 1: Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher irAE (except endocrine disorders that can be treated with replacement therapy) or was discontinued from that treatment due to Grade 2 myocarditis or recurrent Grade 2 pneumonitis
* Arm 2: Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137)
* Arm 2: Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their advanced or metastatic NSCLC
* Arm 2: Has received radiation therapy to the lung that is \>30 Gy within 6 months of the first dose of study intervention
* Received prior systemic anticancer therapy including investigational agents within 4 weeks before allocation
* Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids
* Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
* Requires treatment with a strong inhibitor or inducer of CYP3A4 at least 14 days before the first dose of study intervention and throughout the study
* Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
* Arm 2: Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
* Arm 2: Active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid)
* Known additional malignancy that is progressing or has required active treatment within the past 3 years
* Known active CNS metastases and/or carcinomatous meningitis
* History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Active infection requiring systemic therapy
* History of HIV infection
* Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection
* History or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator
* Known psychiatric or substance abuse disorder
* A severe hypersensitivity reaction to treatment a monoclonal antibody/component of the study intervention

Primary outcomes:
measure: Number of Participants Experiencing Dose-Limiting Toxicity (DLT)
timeFrame: Up to 21 days after each dose
measure: Number of Participants Experiencing ≥1 Adverse Event (AE)
timeFrame: Up to ~25 months
measure: Number of Participants Discontinuing from Study Therapy due to AE
timeFrame: Up to ~25 months
Secondary outcomes:
measure: Area Under the Plasma Concentration-Time Curve (AUC) of sacituzumab tirumotecan -Antibody-Drug Conjugate (sacituzumab tirumotecan ADC)
timeFrame: Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
measure: Maximum Plasma Concentration (Cmax) of sacituzumab tirumotecan-ADC
timeFrame: Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
measure: Minimum Plasma Concentration (Cmin) of sacituzumab tirumotecan-ADC
timeFrame: Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
measure: Apparent terminal half-life (t½) of sacituzumab tirumotecan-ADC
timeFrame: Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
measure: Time to Maximum Plasma Concentration (Tmax) of sacituzumab tirumotecan-ADC
timeFrame: Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
measure: Clearance (CL) of sacituzumab tirumotecan-ADC
timeFrame: Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
measure: Volume of Distribution (Vz) of sacituzumab tirumotecan-ADC
timeFrame: Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
measure: Accumulation Ratio (Rac) of sacituzumab tirumotecan-ADC
timeFrame: Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
measure: Area Under the Plasma AUC of sacituzumab tirumotecan-Total Antibody (sacituzumab tirumotecan-TAB)
timeFrame: Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
measure: Cmax of sacituzumab tirumotecan-TAB
timeFrame: Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
measure: Cmin of sacituzumab tirumotecan-TAB
timeFrame: Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
measure: t½ of sacituzumab tirumotecan-TAB
timeFrame: Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
measure: Tmax of sacituzumab tirumotecan-TAB
timeFrame: Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
measure: CL of sacituzumab tirumotecan-TAB
timeFrame: Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
measure: Vz of sacituzumab tirumotecan-TAB
timeFrame: Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
measure: Rac of sacituzumab tirumotecan-TAB
timeFrame: Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
measure: Cmax of sacituzumab tirumotecan-ADC Coadministered with Pembrolizumab
timeFrame: Cycle 1 and 2: Days 1 and 29 preinfusion and 0.5 hours postinfusion (each cycle is 29 days)
measure: Cmin of sacituzumab tirumotecan-ADC Coadministered with Pembrolizumab
timeFrame: Cycle 1 and 2: Days 1 and 29 preinfusion and 0.5 hours postinfusion (each cycle is 29 days)
measure: Rac of sacituzumab tirumotecan-ADC Coadministered with Pembrolizumab
timeFrame: Cycle 1 and 2: Days 1 and 29 preinfusion and 0.5 hours postinfusion (each cycle is 29 days)
measure: Cmax of sacituzumab tirumotecan-TAB Coadministered with Pembrolizumab
timeFrame: Cycle 1 and 2: Days 1 and 29 preinfusion and 0.5 hours postinfusion (each cycle is 29 days)
measure: Cmin of sacituzumab tirumotecan-TAB Coadministered with Pembrolizumab
timeFrame: Cycle 1 and 2: Days 1 and 29 preinfusion and 0.5 hours postinfusion (each cycle is 29 days)
measure: Rac of sacituzumab tirumotecan-TAB Coadministered with Pembrolizumab
timeFrame: Cycle 1 and 2: Days 1 and 29 preinfusion and 0.5 hours postinfusion (each cycle is 29 days)
measure: Cmax of KL610023 Coadministered with Pembrolizumab
timeFrame: Cycle 1 and 2: Days 1 and 29 preinfusion and 0.5 hours postinfusion (each cycle is 29 days)
measure: Rac of KL610023 Coadministered with Pembrolizumab
timeFrame: Cycle 1 and 2: Days 1 and 29 preinfusion and 0.5 hours postinfusion (each cycle is 29 days)
measure: Objective Response Rate (ORR)
timeFrame: Up to ~25 months
measure: Duration of Response (DOR)
timeFrame: Up to ~25 months
measure: Incidence of Antidrug Antibodies (ADA) to sacituzumab tirumotecan
timeFrame: Up to ~25 months
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Aichi Cancer Center Hospital ( Site 0006)
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East ( Site 0002)
state: Chiba
city: Matsuyama
country: Japan
facility: National Hospital Organization Shikoku Cancer Center ( Site 0008)
state: Ehime
city: Yokohama
country: Japan
facility: Kanagawa cancer center-Department of Thoracic Oncology ( Site 0004)
state: Kanagawa
city: Hirakata
country: Japan
facility: Kansai Medical University Hospital ( Site 0007)
state: Osaka
city: Nagaizumi-cho,Sunto-gun
country: Japan
facility: Shizuoka Cancer Center ( Site 0005)
state: Shizuoka
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital ( Site 0001)
state: Tokyo
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: