Sacituzumab Tirumotecan (MK-2870) as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors (MK-2870-008)

NCT06049212 | Active Not Recruiting Phase 1

• 2 other identifiers: 2870-008jRCT2031230356
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 7

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.

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)

Outcome Measures

Primary Outcomes (3)

• Number of Participants Experiencing Dose-Limiting Toxicity (DLT)

  A DLT is defined as any of the following: Grade 4 nonhematologic toxicity; Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia or lymphopenia; any nonhematologic AE ≥Grade 3 in severity (with some exceptions); any Grade 3 or Grade 4 nonhematologic laboratory value (if certain criteria are met); febrile neutropenia Grade 3 or Grade 4; a prolonged delay (\>2 weeks) in initiating sacituzumab tirumotecan second dose due to intervention-related toxicity; any intervention-related toxicity that causes the participant to discontinue intervention during DLT evaluation period; or any Grade 5 toxicity. All toxicities will be graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0.

  Up to 21 days after each dose

• Number of Participants Experiencing ≥1 Adverse Event (AE)

  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.

  Up to ~32 months

• Number of Participants Discontinuing from Study Therapy due to AE

  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.

  Up to ~32 months

Secondary Outcomes (28)

• Area Under the Plasma Concentration-Time Curve (AUC) of sacituzumab tirumotecan -Antibody-Drug Conjugate (sacituzumab tirumotecan ADC)

  Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion

• Maximum Plasma Concentration (Cmax) of sacituzumab tirumotecan-ADC

  Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion

• Minimum Plasma Concentration (Cmin) of sacituzumab tirumotecan-ADC

  Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion

• Apparent terminal half-life (t½) of sacituzumab tirumotecan-ADC

  Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion

• Time to Maximum Plasma Concentration (Tmax) of sacituzumab tirumotecan-ADC

  Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion

Study Arms (2)

Arm 1: Sacituzumab tirumotecan Monotherapy

EXPERIMENTAL

Participants receive single doses of sacituzumab tirumotecan monotherapy once every 2 weeks (Q2W).

Biological: Sacituzumab tirumotecan; Drug: Supportive care measures

Arm 2: Pembrolizumab + Sacituzumab tirumotecan Combination Therapy

EXPERIMENTAL

Participants receive sacituzumab tirumotecan Q2W in combination with pembrolizumab once every 6 weeks (Q6W).

Biological: Sacituzumab tirumotecan; Biological: Pembrolizumab; Drug: Supportive care measures

Interventions

Pembrolizumab BIOLOGICAL

Pembrolizumab solution for IV infusion.

Also known as: MK-3475

Arm 2: Pembrolizumab + Sacituzumab tirumotecan Combination Therapy

Supportive care measures DRUG

Participants are allowed to take supportive care measures at the discretion of the investigator. Prophylactic supportive care measures may include but are not limited to antiemetic agents, antidiarrheal agents, granulocyte and erythroid growth factors, and blood transfusions

Arm 1: Sacituzumab tirumotecan Monotherapy; Arm 2: Pembrolizumab + Sacituzumab tirumotecan Combination Therapy

Sacituzumab tirumotecan BIOLOGICAL

Sacituzumab tirumotecan injection powder for intravenous (IV) infusion.

Also known as: SKB264, MK-2870

Arm 1: Sacituzumab tirumotecan Monotherapy; Arm 2: Pembrolizumab + Sacituzumab tirumotecan Combination Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 severe 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (7)

Aichi Cancer Center ( Site 0006)

Nagoya, Aichi-ken, 464-8681, Japan

Location

National Cancer Center Hospital East ( Site 0002)

Kashiwa, Chiba, 277-8577, Japan

Location

National Hospital Organization Shikoku Cancer Center ( Site 0008)

Matsuyama, Ehime, 791-0280, Japan

Location

Kanagawa Cancer Center ( Site 0004)

Yokohama, Kanagawa, 241-8515, Japan

Location

Kansai Medical University Hospital ( Site 0007)

Hirakata, Osaka, 573-1191, Japan

Location

Shizuoka Cancer Center ( Site 0005)

Nagaizumi-cho,Sunto-gun, Shizuoka, 411-8777, Japan

Location

National Cancer Center Hospital ( Site 0001)

Chuo-ku, Tokyo, 104-0045, Japan

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2023
• First Posted: September 22, 2023
• Study Start: October 26, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): January 29, 2027
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

JP (7)