Evaluation of Pembrolizumab, Patritumab Deruxtecan, and Drug Combinations in Stage IV Non-Small Cell Lung Cancer: A Phase 2 Umbrella Study

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What is this study about?

This clinical trial is focused on studying treatments for Stage IV non-small cell lung cancer (NSCLC), a type of lung cancer that has spread to other parts of the body. The study will explore the effectiveness and safety of different treatment combinations. One of the main treatments being tested is pembrolizumab, also known by its code name MK-3475. Pembrolizumab is a type of medication that helps the immune system fight cancer cells. Other treatments being studied in combination with pembrolizumab include patritumab deruxtecan (code name MK-1022), paclitaxel, pemetrexed disodium, carboplatin, and paclitaxel albumin-bound.

The purpose of this study is to evaluate how well these treatment combinations work and how safe they are for patients. Participants will receive these treatments through an intravenous infusion, which means the medication is given directly into a vein. The study will monitor the participants’ response to the treatments and any side effects they may experience. The goal is to find the most effective and safe treatment options for patients with Stage IV NSCLC.

Throughout the study, researchers will assess the Objective Response Rate (ORR), which measures how well the cancer responds to the treatment. They will also track the number of participants who experience side effects and those who may need to stop the treatment due to these effects. Additionally, the study will look at the Duration of Response (DOR), Progression-Free Survival (PFS), and Overall Survival (OS) to understand the long-term benefits of the treatments. This research aims to improve treatment options for patients with advanced lung cancer.

1 enrollment and consent

after joining the study, you will sign a consent form that explains the purpose of the trial and the procedures involved.

baseline assessments, including medical history, physical exam, laboratory tests, and imaging studies, will be performed to document your condition before any treatment.

2 initial treatment administration

the first treatment cycle begins with an intravenous (iv) infusion of pembrolizumab 200 mg.

depending on the specific study arm, you may also receive one or more of the following chemotherapy drugs by iv infusion:

paclitaxel 500 mg, pemetrexed 1250 mg, carboplatin 900 mg, or paclitaxel albumin‑bound 250 mg.

if assigned to the investigational arm, you will receive patritumab deruxtecan (mk‑1022) at the dose defined by the protocol.

3 repeated treatment cycles

treatment cycles are repeated according to the schedule set by the study protocol, typically every few weeks.

each cycle includes the same iv infusions of pembrolizumab 200 mg and the chemotherapy agents or investigational drug assigned to you.

the exact number of cycles will be determined by your response to therapy and any side effects that may occur.

4 safety monitoring

regular clinic visits are scheduled to check vital signs, perform laboratory tests, and assess any adverse events (side effects).

the study staff will record any symptoms you experience and may adjust treatment if necessary to ensure safety.

5 tumor response assessment

imaging studies (such as CT scans) are performed at predefined intervals to evaluate the effect of treatment on the tumor.

the primary goal is to determine the objective response rate, which measures how much the tumor shrinks or disappears.

6 treatment discontinuation

treatment may be stopped if you experience unacceptable toxicity, if the disease progresses, or if you choose to withdraw from the study.

the decision to discontinue is made based on clinical judgment and the criteria outlined in the protocol.

7 post‑treatment follow‑up

after the last dose of study medication, you will continue to have periodic visits to monitor overall survival, progression‑free survival, and any long‑term side effects.

these follow‑up visits help researchers understand the durability of the treatment response.

Who Can Join the Study?

Confirmed diagnosis of Stage IV non‑small cell lung cancer (NSCLC), either squamous or non‑squamous type, verified by laboratory examination of tumor cells (histology or cytology) according to the American Joint Committee on Cancer (AJCC) staging system version 8.
Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale, meaning you are fully active (0) or able to carry out light work (1) as assessed within the week before enrollment.
Availability of a tumor tissue sample, either from an existing (archival) specimen or from a new core, incisional, or excisional biopsy of a tumor that has not been treated with radiation.
If you are living with human immunodeficiency virus (HIV), your infection must be well controlled while you are taking antiretroviral therapy (ART).
If you test positive for hepatitis B surface antigen (HBsAg), you must have been on hepatitis B virus (HBV) antiviral medication for at least four weeks and have an undetectable HBV viral load (no detectable virus in blood) before randomization.
Both men and women are eligible to participate.

Who Cannot Join the Study?

Having a type of lung cancer called small cell lung cancer or a mixed tumor that contains small cell parts.
Having uncontrolled chest pain from heart disease (angina) within the last 6 months.
Having an irregular heartbeat (arrhythmia) that needs ongoing medication.
Having a history of serious fast heart rhythms from the lower chambers of the heart, such as ventricular tachycardia, ventricular fibrillation, or a rhythm called Torsade de Pointes.
Having a slow heartbeat (less than 50 beats per minute) unless you have a pacemaker (a device that keeps the heart beating regularly).
Having a history of second- or third-degree heart block (a type of severe heartbeat interruption). You may be allowed if you now have a pacemaker and no fainting or serious rhythm problems.
Having heart or blood‑vessel bypass surgery within the last 6 months.
Having a complete left bundle branch block (a pattern of abnormal electrical activity in the heart).
Not having enough time off (washout period) from previous medicines as required by the study.
Having previously taken a drug that blocks topoisomerase I (an enzyme that helps cancer cells copy DNA) or an experimental antibody that targets HER3 and contains a special chemotherapy piece called an exatecan derivative.
Having already received systemic (whole‑body) cancer treatment for your metastatic lung cancer.
If your tumor is of the squamous type and has certain genetic changes (mutations in EGFR, rearrangements in ALK or ROS1), you cannot join.
Having previously received any medication that blocks the immune checkpoints PD‑1, PD‑L1, or PD‑L2, or other drugs that affect T‑cell receptors.
Having radiation treatment within 2 weeks before randomization, or having radiation‑related side effects that need steroids, or having radiation‑induced lung inflammation (radiation pneumonitis).
Having received lung radiation of more than 30 gray (a measure of radiation dose) within the last 6 months.
Having received a live or weakened‑virus vaccine within 30 days before the first study dose.
Having an immune system problem or taking strong steroids or other immune‑suppressing medicines within 7 days before the first study dose.
Having another cancer that is getting worse or needed active treatment in the past 3 years.
Having active cancer spread to the brain or spinal fluid (central nervous system metastases or carcinomatous meningitis).
Being severely allergic to any of the study drugs or their inactive ingredients.
Having an active autoimmune disease (where the body attacks itself) that needed systemic treatment in the past 2 years.
Having an active infection that requires medication.
Being infected with HIV and having a history of Kaposi’s sarcoma or Multicentric Castleman’s disease.
Having both active Hepatitis B and Hepatitis C infections at the same time.
Not having fully recovered from major surgery or still having surgery‑related problems.
Having severe lung problems from other illnesses, including any underlying lung disease or autoimmune/inflammatory disorders that affect the lungs.
Having cancer cells in the thin membranes covering the brain and spinal cord (leptomeningeal disease).
Having a history of, or current, neurologic paraneoplastic syndrome (a nerve disorder caused by cancer).
Having serious disease of the cornea (the clear front part of the eye).
Having had a heart attack (myocardial infarction) within the last 6 months.
Having moderate to severe heart failure classified as NYHA Class 3 or 4 (significant limitation of physical activity).

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Koranyi National Institute For Pulmonology	Budapest	Hungary
Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome	Italy
Szpital Wojewodzki Im. Mikolaja Kopernika W Koszalinie	Koszalin	Poland

Other Sites

Site Name	City	Country
Ospedale San Raffaele S.r.l.	Milan	Italy
Hospital Clinic De Barcelona	Barcelona	Spain
Hospital Universitario Quironsalud Madrid	Pozuelo De Alarcon	Spain
Wielkopolskie Centrum Pulmonologii I Torakochirurgii Im. Eugenii I Janusza Zeylandow	Poznan	Poland
Jasz-Nagykun-Szolnok Varmegyei Hetenyi Geza Korhaz-Rendelointezet	Szolnok	Hungary
Fondazione I.R.C.C.S. Istituto Neurologico Besta	Milan	Italy
Lgjyy Gyzdluf Hzrzqqyz Oz Ahpbfl	Athens	Greece
Ghtlowuvoxaojwmir Vnzzhiaia Pvwj Ajqmhl Etrwvmkl Orazep Kckkld	Gyor	Hungary
Aituhd Mpuhfnd Csuitb Siti	Thessaloniki	Greece
Ntfatcek Ibkeohqk Oytvygndu Ivc Mtxor Sgdlyytmblyztcbmdutdbsozychk Idtnstah Bgwsvuis	Cracow	Poland
Uxafjppojlqayj Cclumyc Kgncqbfmv	Gdansk	Poland
Iuftjjcx Coqdod Dxpriglywtqtaabra	L'hospitalet De Llobregat	Spain

Trial status

Country	Status	Recruitment Start
Greece	Not recruiting	27.01.2025
Hungary	Not recruiting	27.01.2025
Italy	Not recruiting	27.01.2025
Poland	Not recruiting	27.01.2025
Spain	Not recruiting	27.01.2025

Trial locations

Investigated drugs:

KEYTRUDA (pembrolizumab)
KEYTRUDA is an immunotherapy drug that helps the body’s own immune system find and attack lung cancer cells. In this study it is given through an IV and is combined with other medicines to see how well it works as a first‑line treatment for stage IV non‑small cell lung cancer.

MK‑1022 (patritumab deruxtecan)
MK‑1022 is an experimental medicine that attaches a chemotherapy payload to an antibody that seeks out a protein called HER3 on cancer cells. This design aims to deliver the chemotherapy directly to the tumor while sparing healthy tissue. It is being tested in combination with KEYTRUDA, with or without additional chemotherapy.

Paclitaxel
Paclitaxel is a chemotherapy drug that stops cancer cells from dividing by interfering with their internal skeleton. In the trial it is given by IV and serves as a standard chemotherapy partner to compare the new combinations against.

Pemetrexed
Pemetrexed is a chemotherapy that blocks the building blocks needed for DNA and RNA, which prevents cancer cells from growing and multiplying. It is used in the study as part of a standard chemotherapy regimen to see how the new treatments perform alongside it.

Carboplatin
Carboplatin is a platinum‑based chemotherapy that damages the DNA inside cancer cells, leading to cell death. In this trial it is combined with other drugs to represent a typical chemotherapy backbone for comparison.

Paclitaxel albumin‑bound (nab‑paclitaxel)
This is a special form of paclitaxel that is attached to albumin, a protein that helps the drug travel more easily into tumors. It is given through an IV and is used as another standard chemotherapy option to compare with the investigational treatment combinations.

Investigated diseases:

Lung neoplasm malignant

Stage IV non‑small cell lung cancer – This disease is a type of lung cancer that begins in the cells lining the airways and does not have the small cell appearance under a microscope. It grows slowly enough to form a solid mass that can block air flow and cause coughing or breathlessness. As it advances, cancer cells can break away from the original tumor and travel through the bloodstream or lymph system to other parts of the body. In stage IV, these secondary tumors are found in distant organs such as the brain, bones, liver, or opposite lung. The condition continues to progress as the new tumors increase in size and may affect the function of the organs where they settle.

Trial ID:

2024-515772-12-00

Protocol code:

MK-3475-01G

Trial Phase:

Therapeutic exploratory (Phase II)

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Evaluation of Pembrolizumab, Patritumab Deruxtecan, and Drug Combinations in Stage IV Non-Small Cell Lung Cancer: A Phase 2 Umbrella Study

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?