## Protocol Section
### Identification Module
**NCT ID:** NCT06422143

**Brief Title:** Pembrolizumab With or Without Maintenance Sacituzumab Tirumotecan (Sac-TMT; MK-2870) in Metastatic Squamous Non-small Cell Lung Cancer (NSCLC) [MK-2870-023]

**Official Title:** Phase 3 Study of Pembrolizumab in Combination With Carboplatin/Taxane (Paclitaxel or Nab-paclitaxel) Followed by Pembrolizumab With or Without Maintenance MK-2870 in the First-line Treatment of Metastatic Squamous Non-small Cell Lung Cancer

#### Organization Study ID Info
**ID:** 2870-023
#### Organization
**Class:** INDUSTRY
**Full Name:** Merck Sharp & Dohme LLC
#### Secondary ID Infos
**Domain:** EU CT
**ID:** 2023-510128-66
**Type:** OTHER
**Domain:** UTN
**ID:** U1111-1301-2790
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2031-02-12

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-20

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-15

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2029-01-12

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-07-02

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-20
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-15
**Study First Submit QC Date:** 2024-05-15
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Merck Sharp & Dohme LLC

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** This is a phase 3 study of pembrolizumab in combination with carboplatin/taxane (paclitaxel or nab-paclitaxel) followed by pembrolizumab with or without maintenance sacituzumab tirumotecan (sac-TMT; MK-2870) in first-line treatment of metastatic squamous non-small cell lung cancer. It is hypothesized that pembrolizumab with maintenance sacituzumab tirumotecan is superior to pembrolizumab without sacituzumab tirumotecan maintenance with respect to overall survival (OS).

**Detailed Description:** All participants undergo an initial induction phase of four cycles, each cycle consisting of a 3-week cycle of pembrolizumab q3w + carboplatin q3w + paclitaxel q3w or nabpaclitaxel weekly. Participants are then randomly assigned to pembrolizumab maintenance vs. pembrolizumab + sac-TMT maintenance.

### Conditions Module

**Conditions:**

- Non-small Cell Lung Cancer

- NSCLC

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** Participants are allocated to a single induction arm, then assigned randomly to one of 2 maintenance arms.

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 851

**Type:** ESTIMATED

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** During the Induction phase, participants receive pembrolizumab 200 mg q3w for 4 cycles, carboplatin AUC 6 (mg/mL/min) q3w for 4 cycles, and paclitaxel 200 mg/m2 q3w for 4 cycles or nab-paclitaxel 100 mg/m2 weekly for 4 cycles. During the Maintenance phase, participants receive sac-TMT 4 mg/kg infusion every 2 weeks (q2w) after receipt of an antihistamine, H2 receptor antagonist, acetaminophen (or equivalent), and dexamethasone (or equivalent) until discontinuation criteria is met for sac-TMT; and pembrolizumab 400 mg every 6 weeks (q6w) for 96 weeks.

**Intervention Names:**

- Biological: Pembrolizumab

- Biological: sac-TMT

**Label:** Maintenance Arm 1: Pembrolizumab + sac-TMT

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** During the induction phase, participants receive pembrolizumab 200 mg q3w for 4 cycles, carboplatin AUC 6 (mg/mL/min) q3w for 4 cycles, and paclitaxel 200 mg/m2 q3w for 4 cycles or nab-paclitaxel 100 mg/m2 weekly for 4 cycles. During the Maintenance phase, participants receive pembrolizumab 400 mg q6w for 96 weeks.

**Intervention Names:**

- Biological: Pembrolizumab

**Label:** Maintenance Arm 2: Pembrolizumab Monotherapy

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Maintenance Arm 1: Pembrolizumab + sac-TMT

- Maintenance Arm 2: Pembrolizumab Monotherapy

**Description:** Intravenous (IV) infusion

**Name:** Pembrolizumab

**Other Names:**

- KEYTRUDA®

- MK-3475

- SCH 900475

**Type:** BIOLOGICAL

#### Intervention 2

**Arm Group Labels:**

- Maintenance Arm 1: Pembrolizumab + sac-TMT

**Description:** IV infusion

**Name:** sac-TMT

**Other Names:**

- MK-2870

- Sacituzumab tirumotecan

**Type:** BIOLOGICAL

### Outcomes Module

#### Primary Outcomes

**Description:** OS is the time from randomization to death due to any cause.

**Measure:** Overall survival (OS)

**Time Frame:** Up to ~79 months

#### Secondary Outcomes

**Description:** PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1).

**Measure:** Progression-Free Survival (PFS)

**Time Frame:** Up to ~79 months

**Description:** 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.

**Measure:** Number of participants with ≥1 adverse event (AE)

**Time Frame:** Up to ~79 months

**Description:** 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.

**Measure:** Number of participants discontinuing from study therapy due to AE(s)

**Time Frame:** Up to ~79 months

**Description:** European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) is a 30-item scale to assess the overall quality of life in cancer patients. The global health status and QoL scores are based on participant responses to items 29 ("How would you rate your overall health during past week?") and 30 ("How would you rate your overall quality of life during the week?") that are scored on a 7-point scale (1 = "Very poor" to 7 = "Excellent"). Higher scores indicate better overall health status.

**Measure:** Change in Score from Baseline to a Predefined Timepoint in Participant-Reported Global health status/Quality of Life (QoL) Score (EORTC QLQ-C30 Items 29 and 30)

**Time Frame:** Baseline and up to ~79 months

**Description:** EORTC QLQ-C30 is a 30-item scale to assess the overall quality of life of cancer patients. The dyspnea score is based on participant responses to item 8 ("Were you short of breath?") that is scored on a 4-point scale (1 = 'Not at All' to 4 = 'Very Much'). Higher scores indicate worse dyspnea symptoms.

**Measure:** Change in Score from Baseline to a Predefined Timepoint in Participant-Reported Dyspnea (EORTC QLQ-C30 Item 8)

**Time Frame:** Baseline and up to ~79 months

**Description:** EORTC QLQ-C13 is a 13-item addendum to EORTC QLQ-C30 to assess the overall quality of life of lung cancer patients. The cough score is based on participant responses to item 31 ("How much did you cough?") that is scored on a 4-point scale (1 = 'Not at All' to 4 = 'Very Much'). Higher scores indicate worse cough.

**Measure:** Change in Score from Baseline to a Predefined Timepoint in Participant-Reported Cough (EORTC QLQ-LC13 Item 31)

**Time Frame:** Baseline and up to ~79 months

**Description:** EORTC QLQ-C13 is a 13-item addendum to EORTC QLQ-C30 to assess the overall quality of life of lung cancer patients. The chest pain score is based on participant responses to item 40 e (1 = "Not at All" to 4 = "Very Much").

**Measure:** Change in Score from Baseline to a Predefined Timepoint in Participant-Reported Chest Pain (EORTC QLQ-LC13 Item 40)

**Time Frame:** Baseline and up to ~79 months

**Description:** EORTC QLQ-C30 is a 30-item scale to assess the overall quality of life in cancer patients. TTD in global health status and QoL scores are based on participant responses to items 29 ("How would you rate your overall health during past week?") and 30 ("How would you rate your overall quality of life during the week?") that are scored on a 7-point scale (1 = "Very poor" to 7 = "Excellent"). Higher scores indicate better overall health status.

**Measure:** Time to First Deterioration (TTD) in Global Health Status/QoL Scores (EORTC QLQ-C30 Items 29 and 30)

**Time Frame:** Up to ~79 months

**Description:** EORTC QLQ-C30 is a 30-item scale to assess the overall quality of life of cancer patients. TTD in dyspnea score is based on participant responses to item 8 ("Were you short of breath?") that is scored on a 4-point scale (1 = 'Not at All' to 4 = 'Very Much'). Higher scores indicate worse dyspnea symptoms.

**Measure:** TTD in Dyspnea Score (EORTC QLQ-C30 Item 8)

**Time Frame:** Up to ~79 months

**Description:** EORTC QLQ-C13 is a 13-item addendum to EORTC QLQ-C30 to assess the overall quality of life of lung cancer patients. TTD in cough score is based on participant responses to item 31 ("How much did you cough?") that is scored on a 4-point scale (1 = 'Not at All' to 4 = 'Very Much'). Higher scores indicate worse cough.

**Measure:** TTD in Cough (EORTC QLQ-LC13 Item 31)

**Time Frame:** Up to ~79 months

**Description:** EORTC QLQ-C13 is a 13-item addendum to EORTC QLQ-C30 to assess the overall quality of life of lung cancer patients. TTD in chest pain score is based on participant responses to item 40 ("Have you had pain in your chest?") that is scored on a 4-point scale (1 = 'Not at All' to 4 = 'Very Much'). Higher scores indicate worse chest pain.

**Measure:** TTD in Chest Pain (EORTC QLQ-LC13 Item 40)

**Time Frame:** Up to ~79 months

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Histologically or cytologically confirmed diagnosis of squamous squamous non-small cell lung cancer (NSCLC) \[Stage IV: M1a, M1b, M1c, American Joint Committee on Cancer Staging Manual, version 8\]
* Measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology
* Has life expectancy ≥3 months
* Has Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1 assessed within 7 days prior to allocation
* Archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated has been provided
* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
* Participants who are hepatitis B surface antigen (HBsAg)-positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load before allocation
* Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
* Participants who have adverse events (AEs) due to previous anticancer therapies must have recovered to ≤ Grade 1 or baseline (participants with endocrine-related AEs who are adequately treated with hormone replacement are eligible)
* Has adequate organ function
* For Maintenance only (prior to randomization): is without disease progression of their NSCLC, as determined by BICR using RECIST 1.1 after completion of study-specified Induction with an evaluable scan at Week 12
* For Maintenance only (prior to randomization): has ECOG PS of 0 or 1 as assessed at the Prerandomization Visit
* For Maintenance only (prior to randomization): all AEs (with the exception of alopecia, Grade 2 fatigue, and Grade ≤2 endocrine-related AEs requiring treatment or hormone replacement) have recovered
* For Maintenance only (prior to randomization): has adequate organ function

Exclusion Criteria:

* Diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements
* Grade ≥2 peripheral neuropathy
* History of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing
* 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 other serious cardiovascular and cerebrovascular diseases within 6 months before study intervention
* HIV-infected participants who have been newly diagnosed or with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Received prior systemic anticancer therapy for their metastatic NSCLC
* 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, cytotoxic Tlymphocyte-associated protein 4, OX-40, CD137) \[Note: Prior treatment with chemotherapy and/or radiation as a part of neoadjuvant or adjuvant therapy or chemoradiation therapy for nonmetastatic NSCLC is allowed as long as therapy was completed at least 12 months before diagnosis of metastatic NSCLC.\]
* Received prior treatment with a TROP2-targeted antidrug conjugate (ADC)
* Received prior systemic anticancer therapy including investigational agents within 4 weeks before allocation
* Received radiation therapy to the lung that is \>30 Gray within 6 months of start of study intervention
* 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
* Active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
* Participants who have not adequately recovered from major surgery or have ongoing surgical complications
* Received prior treatment with a topoisomerase I inhibitor-containing ADC
* Is currently receiving a strong inducer/inhibitor of CYP3A4 that cannot be discontinued for the duration of the study (the required washout period before starting sac-TMT is 2 weeks)
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
* Has known CNS metastases/carcinomatous meningitis (participants with previously treated brain metastases may participate provided they are clinically stable for t least 2 weeks and, have no evidence of new or enlarging brain metastases and also are off steroids 3 days prior to dosing with study medication. Subjects with known untreated, asymptomatic brain metastases \[ie, no neurological symptoms, no requirements for corticosteroids, no or minimal surrounding edema, and no lesion \>1.5 cm\] may participate but will require regular imaging of the brain as a site of disease)
* Severe hypersensitivity (≥Grade 3) to study intervention and/or any of its excipients or to another biologic therapy
* Active autoimmune disease that has required systemic treatment in the past 2 years (replacement therapy \[eg, thyroxine, insulin, or physiologic corticosteroid\] is allowed)
* History of (noninfectious)pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Active infection requiring systemic therapy
* History of allogeneic tissue/solid organ transplant

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### IPD Sharing Statement Module

**Description:** http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

**IPD Sharing:** YES

**URL:** http://engagezone.msd.com/ds_documentation.php

### References Module

#### See Also Links

**Label:** Merck Clinical Trials Information

**URL:** https://www.merckclinicaltrials.com/

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000012142

- Term: Respiratory Tract Neoplasms

- ID: D000013899

- Term: Thoracic Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000008171

- Term: Lung Diseases

- ID: D000012140

- Term: Respiratory Tract Diseases

- ID: D000002283

- Term: Carcinoma, Bronchogenic

- ID: D000001984

- Term: Bronchial Neoplasms

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M5546

- Name: Carcinoma, Non-Small-Cell Lung

- Relevance: HIGH

- As Found: Non-Small Cell Lung Cancer

- ID: M11172

- Name: Lung Neoplasms

- Relevance: HIGH

- As Found: Lung Cancer

- ID: M5534

- Name: Carcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M14979

- Name: Respiratory Tract Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M16658

- Name: Thoracic Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M11168

- Name: Lung Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5540

- Name: Carcinoma, Bronchogenic

- Relevance: LOW

- As Found: Unknown

- ID: M5260

- Name: Bronchial Neoplasms

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000008175

- Term: Lung Neoplasms

- ID: D000002289

- Term: Carcinoma, Non-Small-Cell Lung

### Intervention Browse Module - Ancestors

- ID: D000074322

- Term: Antineoplastic Agents, Immunological

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000082082

- Term: Immune Checkpoint Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Infl

- Name: Anti-Inflammatory Agents

- Abbrev: AnEm

- Name: Antiemetics

- Abbrev: Gast

- Name: Gastrointestinal Agents

- Abbrev: Antipy

- Name: Antipyretics

- Abbrev: Analg

- Name: Analgesics

### Intervention Browse Module - Browse Leaves

- ID: M19537

- Name: Paclitaxel

- Relevance: LOW

- As Found: Unknown

- ID: M18650

- Name: Carboplatin

- Relevance: LOW

- As Found: Unknown

- ID: M7102

- Name: Dexamethasone

- Relevance: LOW

- As Found: Unknown

- ID: M2340

- Name: Acetaminophen

- Relevance: LOW

- As Found: Unknown

- ID: M349416

- Name: Pembrolizumab

- Relevance: HIGH

- As Found: Blind

- ID: M231

- Name: Albumin-Bound Paclitaxel

- Relevance: LOW

- As Found: Unknown

- ID: M235549

- Name: Dexamethasone acetate

- Relevance: LOW

- As Found: Unknown

- ID: M9709

- Name: Histamine Antagonists

- Relevance: LOW

- As Found: Unknown

- ID: M9710

- Name: Histamine H1 Antagonists

- Relevance: LOW

- As Found: Unknown

- ID: M147959

- Name: Taxane

- Relevance: LOW

- As Found: Unknown

- ID: M9711

- Name: Histamine H2 Antagonists

- Relevance: LOW

- As Found: Unknown

- ID: M1346

- Name: Antineoplastic Agents, Immunological

- Relevance: LOW

- As Found: Unknown

- ID: M2342

- Name: Immune Checkpoint Inhibitors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: C000582435

- Term: Pembrolizumab

### Misc Info Module

- Version Holder: 2024-05-31
