Plasma-Adapted First-Line Pembro In NSCLC

NCT04166487 | Active Not Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: 19-523
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 5

Brief Summary

This research study is studying to see if a blood test, collected at different times during the treatment of metastatic non-small lung cancer, can be used to detect early response in patients being treated with pembrolizumab and use that information to determine whether patients should continue treatment with pembrolizumab or switch treatment to pembrolizumab in combination with chemotherapy. The names of the study drugs involved in this study are:

• Pembrolizumab
• Platinum doublet chemotherapy, which may include the following:
• Carboplatin and pemetrexed
• Carboplatin and paclitaxel The name of the blood test: \- InVision (Inivata, Ltd.)

Conditions

Metastatic Non-Small Cell Lung Cancer; NSCLC Stage IV

Keywords

NSCLC Stage IV; Metastatic Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 6-month Progression Free Survival rate

  Kaplan-Meier method

  6 Months

Secondary Outcomes (4)

• Early Plasma Response

  42 Days (each cycle is 21 days)

• Progression Free Survival

  he time from registration to the earlier of progression or death due to any cause or 30 Months

• Overall Survival

  time from registration to death from any cause, and patients who are thought to be alive at the time of final analysis will be censored at the last date of contact or 30 months

• Feasibility-adherence to protocol therapy for 4 cycles

  84 Days (each cycle is 21 days)

Study Arms (3)

Pembrolizumab Cycles 1-2

EXPERIMENTAL

* For the first two cycles, Pembrolizumab will be administered at a predetermined dose every 3 weeks. * InVision plasma draw will take place at Cycle 1 Day 1 and Cycle 2 Day 1, with return of results to the treating oncologist prior to Cycle 3 Day 1. * At Cycle 3, patients will be re-registered per the inclusion criteria into 3 arms; * PEMBROLIZUMAB Alone * PEMBROLIZUMAB + Doublet Chemotherapy

Drug: Pembrolizumab; Diagnostic Test: InVision

Pembrolizumab Alone, Cycle 3+

EXPERIMENTAL

\- Following imaging assessment at Cycle 3, participants will continue pembrolizumab alone if the following responses are observed: * Response of Partial Response/Complete Response * Response of Stable Disease with plasma response * Response of Progressive Disease without worsening cancer symptoms AND plasma response

Drug: Pembrolizumab

Pembrolizumab + Doublet Chemotherapy, Cycles 3+

EXPERIMENTAL

* Following imaging assessment at Cycle 3, participants will receive pembrolizumab in combination with platinum doublet chemotherapy if they have a response of stable disease without plasma response, OR no plasma response and response of progressive disease without worsening cancer systems. Platinum doublet should be histology-appropriate and will be given on-label, per treating oncologist. * PEMBROLIZUMAB * Chemotherapy multiple agents systemic * PEMETREXED * CARBOPLATIN * PACLITAXEL

Drug: Pembrolizumab; Drug: PEMETREXED; Drug: CARBOPLATIN; Drug: PACLITAXEL

Interventions

Pembrolizumab DRUG

predetermined dose, once per cycle via IV will be administered every 3 weeks, with 21 consecutive days defined as a treatment cycle.

Also known as: Keytruda®

Pembrolizumab + Doublet Chemotherapy, Cycles 3+; Pembrolizumab Alone, Cycle 3+; Pembrolizumab Cycles 1-2

PEMETREXED DRUG

administered per standard practice, once per cycle via IV will be administered every 3 weeks, with 21 consecutive days defined as a treatment cycle.

Also known as: Alimta®

Pembrolizumab + Doublet Chemotherapy, Cycles 3+

CARBOPLATIN DRUG

administered per standard practice once per cycle via IV will be administered every 3 weeks, with 21 consecutive days defined as a treatment cycle.

Also known as: Paraplatin ®

Pembrolizumab + Doublet Chemotherapy, Cycles 3+

PACLITAXEL DRUG

administered per standard practice once per cycle via IV will be administered every 3 weeks, with 21 consecutive days defined as a treatment cycle.

Also known as: Taxol®,, Onxal

Pembrolizumab + Doublet Chemotherapy, Cycles 3+

InVision DIAGNOSTIC_TEST

Plasma draw for clinical test performed at C1D1 and C2D1; plasma draw for research testing performed at other timepoints per protocol.

Pembrolizumab Cycles 1-2

Eligibility Criteria

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

You may qualify if:

• \- Participants must have histologically or cytologically confirmed stage IV NSCLC (AJCC 8th edition).
• \- Participants must have evaluable disease on imaging per RECIST (measurable disease is not required).
• No prior treatment with a systemic anti-cancer therapy of any kind for the treatment of stage IV NSCLC. Prior definitive chemoradiation for locally advanced disease, or prior adjuvant or neoadjuvant therapy for early stage disease is permitted if completed ≥6 months prior to initiating study treatment.
• Age ≥18 years.
• ECOG performance status 0-2 (see Appendix A)
• Candidate for combination chemoimmunotherapy per physician assessment.
• Participants must have normal organ and marrow function as defined below:
• \-- absolute neutrophil count ≥1000/mcL
• platelets ≥100,000/mcL
• total bilirubin \<1.3 mg/dL
• creatinine \<1.6 mg/dL
• PD-L1 tumor proportion score (TPS) ≥1%, as determined by a CLIA-laboratory.
• The effects of pembrolizumab on the developing human fetus are unknown. For this reason and because immune checkpoint blockade agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of pembrolizumab administration.
• \-- NOTE: a pregnancy test will be required at screening for women of childbearing potential.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Participants with known sensitizing alterations in EGFR, ALK, ROS1 or BRAF.
• Participants who have had chemotherapy or radiotherapy within 1 week prior to entering the study.
• Participants who are receiving any other investigational agents.
• Participants with uncontrolled brain metastases, leptomeningeal disease, or spinal cord compression. Patients with asymptomatic untreated brain metastases are eligible. Patients with treated CNS disease are eligible if stable disease is clinically confirmed ≥2 weeks after definitive CNS therapy (radiation or surgery), and the patient is not receiving systemic steroids ≥10mg of prednisone equivalent at the time of enrollment.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab or other agents used in study.
• Ongoing or active autoimmune disease requiring systemic steroids of ≥10mg of prednisone equivalent or other systemic immunomodulatory agents at the time of enrollment. Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as psoriasis, vitiligo, and alopecia) not requiring systemic therapy, or conditions not expected to recur in the absence of an external trigger are allowed.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because pembrolizumab is a Pregnancy Category D agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with pembrolizumab, breastfeeding should be discontinued if the mother is treated with pembrolizumab. These potential risks may also apply to other agents used in this study.
• Participants with a known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) are excluded from this study.

Sponsors & Collaborators

• Julia K. Rotow, MD: lead
• Inivata: collaborator

Study Sites (5)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Dana-Farber at Steward St. Elizabeth's Medical Center

Brighton, Massachusetts, 02135, United States

Location

Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC) in clinical affiliation with South Shore Hospital

South Weymouth, Massachusetts, 02190, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; Pemetrexed; Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Julia K Rotow, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 13, 2019
• First Posted: November 18, 2019
• Study Start: January 13, 2020
• Primary Completion: June 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (5)