Phase 2 DoceRamPem for Patients With Metastatic or Recurrent NSCLC Who Progressed on Platinum-Doublet and PD-1/PD-L1 Blockade

NCT04340882 | Active Not Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: STUDY00000030NCI-2020-01134WINSHIP4950-20P30CA138292
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

This phase 2 trial will evaluate the safety and efficacy of combining immunotherapy with a PD-1 checkpoint inhibitor (Pembrolizumab), an anti-VEGF receptor (Ramucirumab), and a taxane chemotherapy (Docetaxel) in treating patients with non-small cell lung cancer (NSCLC) who did not respond to FDA-approved treatments with platinum-based chemotherapy given concurrently or sequentially with anti-PD1/PD-L1 immunotherapy. Pembrolizumab helps the body's immune system to attack cancer cells and hinder their ability to grow and spread. Ramucirumab blocks new blood vessel growth to reduce tumor growth. Docetaxel works mainly by stopping cancer cells from dividing. Ramucirumab combined with docetaxel is an FDA-approved therapy for NSCLC patients after progression on platinum-based chemotherapy. It has shown to improve efficacy compared to docetaxel alone in this setting. Pembrolizumab is an FDA-approved treatment for NSCLC and can be given alone or in combination with platinum-based chemotherapy. Investigators hypothesize that the combination of docetaxel, ramucirumab, and pembrolizumab will be safe and more effective than the current standard of care treatments (docetaxel alone or in combination with ramucirumab) in patients with metastatic or recurrent NSCLC after progression on treatment with platinum-based chemotherapy and immunotherapy, given concurrently or sequentially.

Conditions

Metastatic Non-Small Lung Cell Cancer; Recurrent Non-Small Lung Cell Cancer; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8; Stage IV Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• 6-month progression-free survival (PFS) rate

  Will be determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will be reported and its 95% confidence intervals will be estimated using the Clopper-Pearson method. PFS rates of two patient groups stratified by binary biomarker (PD-L1 and KRAS status), respectively will be estimated with the Kaplan-Meier method and compared using the log-rank test, respectively. Cox proportional hazards models will be further used in the multivariable analyses to assess adjusted effect of PD-L1 and KRAS status on the patients' PFS after adjusting for other factors. Interaction terms between these factors will also be tested for statistical significance. The proportional hazards assumption will be evaluated graphically and analytically with regression diagnostics. Violations of the proportional hazards assumptions will be addressed by use of time-dependent covariates or extended Cox regression models.

  up to 6 months

Secondary Outcomes (3)

• Incidence of adverse events

  Up to 30 days after the last dose of study treatment

• Overall response rate

  Through study completion, an average of 1 year

• Overall survival (OS)

  up to 10 years

Study Arms (1)

Treatment (docetaxel, ramucirumab, pembrolizumab)

EXPERIMENTAL

Patients receive docetaxel IV over 60 minutes, ramucirumab IV over 60 minutes, and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Docetaxel; Biological: Pembrolizumab; Biological: Ramucirumab

Interventions

Docetaxel DRUG

Given IV

Also known as: Docecad, RP56976, Taxotere, Taxotere Injection Concentrate

Treatment (docetaxel, ramucirumab, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (docetaxel, ramucirumab, pembrolizumab)

Ramucirumab BIOLOGICAL

Given IV

Also known as: Anti-VEGFR-2 Fully Human Monoclonal Antibody IMC-1121B, Cyramza, IMC-1121B, LY3009806, Monoclonal Antibody HGS-ETR2

Treatment (docetaxel, ramucirumab, pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of non-small cell lung cancer
• Patients must have progressed on a platinum-based chemotherapy and any of the Food and Drug Administration (FDA)-approved PD-1 or PD-L1 immune checkpoint inhibitors, either given sequentially or in combination
• A male participant must agree to use a contraception during the treatment period plus an additional 120 days after the last dose of study treatment and refrain from donating sperm during this period
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days plus 30 days (a menstruation cycle) after the last dose of study treatment
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial
• Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Life expectancy \> 12 weeks as determined by the investigator
• Absolute neutrophil count (ANC) ≥ 1500/uL (collected within 10 days prior to the start of study treatment)
• Platelets ≥ 100 000/uL (collected within 10 days prior to the start of study treatment)
• Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L (collected within 10 days prior to the start of study treatment)
• Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks
• Creatinine ≤ 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) ≥ 30 mL/min for participant with creatinine levels \> 1.5 x institutional ULN (collected within 10 days prior to the start of study treatment)

You may not qualify if:

• A WOCBP with a positive urine pregnancy test within 72 hours prior of the planned treatment on day 1 of each cycle. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Patients have prior exposure to docetaxel or ramucirumab
• Patients with proteinuria of ≥ 2+ on dipsticks or urine protein/creatinine ratio of \> 1 g/24-hour
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks or 5 times the half-life time, whichever is shorter \[could consider shorter interval for kinase inhibitors or other short half-life drugs\] prior to allocation
• Note: Participants must have recovered from all adverse events (AEs) due to previous therapies to grade ≤ 1 or baseline. Participants with grade ≤ 2 neuropathy may be eligible
• Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment
• Has received prior radiotherapy within 1 week of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-central nervous system (CNS) disease
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist) are live attenuated vaccines and are not allowed
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent
• Has a 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 to the first dose of study drug
• Patients with symptomatic brain metastasis (patients with treated brain metastasis without symptoms and not requiring steroid are allowed to participate)
• Has severe hypersensitivity (grade ≥ 3) to pembrolizumab and/or any of its excipients
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients with significant cardiovascular disease (e.g., myocardial infarction, arterial thromboembolism, cerebrovascular thromboembolism) within 6 months prior to start of study therapy; angina requiring therapy; symptomatic peripheral vascular disease; New York Heart Association class 3 or 4 congestive heart failure; or uncontrolled grade ≥ 3 hypertension (diastolic blood pressure ≥ 100 mmHg or systolic blood pressure ≥ 160 mmHg) despite antihypertensive therapy

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: collaborator
• Emory University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Grady Health System

Atlanta, Georgia, 30303, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• Osta BE, Carlisle J, Steuer C, Pakkala S, Leal T, Dhodapkar M, Liu Y, Chen Z, Owonikoko T, Ramalingam S. A Phase 2 Study of Docetaxel, Ramucirumab, and Pembrolizumab for Patients With Metastatic or Recurrent Non-Small-Cell Lung Cancer (NSCLC) who Progressed on Platinum-Doublet and PD-1/PD-L1 Blockade. Clin Lung Cancer. 2022 Nov;23(7):e400-e404. doi: 10.1016/j.cllc.2022.06.003. Epub 2022 Jun 22.

  PMID: 35863963 BACKGROUND

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Docetaxel; pembrolizumab; Ramucirumab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Badi El Osta, MD, FACP

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Phase 2 with initial run-in safety

Study Record Dates

• First Submitted: April 7, 2020
• First Posted: April 10, 2020
• Study Start: June 5, 2020
• Primary Completion (Estimated): September 2, 2026
• Study Completion (Estimated): September 30, 2030
• Last Updated: January 30, 2026

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)