DoceRamPem for Lung Cancer

(DoceRamPem Trial)

Not currently recruiting at 1 trial location

Overseen By Lauren Collins, CCRP

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Pregnancy, Brain metastasis, Cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: Up to 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for people with non-small cell lung cancer (NSCLC) that hasn't responded to standard therapies. The treatment mix includes pembrolizumab, which helps the immune system target cancer cells; ramucirumab, which stops new blood vessels from feeding tumors; and docetaxel, a chemotherapy drug that prevents cancer cells from dividing. Researchers aim to determine if this combination is safe and more effective than current treatments. People with NSCLC who have already tried platinum-based chemotherapy and immunotherapy without success might be good candidates for this study. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group of people, offering a chance to explore new treatment options.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not have received any systemic anti-cancer therapy within 4 weeks before starting the trial. It's best to discuss your current medications with the trial team to get specific guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of docetaxel, ramucirumab, and pembrolizumab is generally safe for patients with non-small cell lung cancer (NSCLC). Previous patients have demonstrated that this combination can be administered without any new safety concerns.

In one study, this combination was well tolerated and showed promising results in NSCLC patients. Another study found that using ramucirumab and docetaxel together had a consistent and manageable safety profile. The FDA has already approved these treatments for certain conditions, indicating a level of safety understanding.

Overall, while all treatments can have side effects, current evidence supports that this combination is safe enough for further testing in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the DoceRamPem treatment because it combines three powerful drugs—docetaxel, ramucirumab, and pembrolizumab—to tackle lung cancer in a new way. Unlike standard treatments that often rely on individual drugs, this combination targets cancer through multiple mechanisms: docetaxel disrupts cell division, ramucirumab prevents the growth of blood vessels that feed tumors, and pembrolizumab boosts the immune system to attack cancer cells. This multi-pronged approach has the potential to enhance effectiveness and overcome resistance that can develop with single-agent therapies.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research has shown that a combination of three drugs—docetaxel, ramucirumab, and pembrolizumab—may help treat non-small cell lung cancer (NSCLC). Participants in this trial will receive this combination treatment. Earlier studies found that patients with advanced NSCLC who had tried other treatments lived longer with this combination. Docetaxel and ramucirumab work well together, extending patient survival compared to docetaxel alone. Adding pembrolizumab to these two drugs has further improved survival rates. These findings suggest that this three-drug combination could be more effective for NSCLC patients who haven't responded to standard treatments. ^{2 4 5 6 7}

Who Is on the Research Team?

Badi El Osta, MD, FACP

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for adults with non-small cell lung cancer (NSCLC) who didn't respond to platinum-based chemo and PD-1/PD-L1 inhibitors. They should have manageable heart conditions, adequate blood counts, measurable disease, agree to contraception use, and not be pregnant or breastfeeding. Prior cancers are okay if they don't affect this study's safety or results. Participants need a life expectancy over 12 weeks and must have recovered from previous cancer treatments.

Inclusion Criteria

My cancer has worsened after treatment with platinum chemotherapy and PD-1/PD-L1 inhibitors.

Your liver enzyme levels are within a certain range, or slightly higher if you have cancer that has spread to the liver.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I haven't had cancer treatment or experimental drugs in the last 4 weeks.

I stopped using immune therapy due to side effects treated with steroids.

Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive docetaxel, ramucirumab, and pembrolizumab intravenously on day 1 of each 21-day cycle until disease progression or unacceptable toxicity

Up to 6 months

1 visit every 21 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with survival follow-up every 12 weeks for 2 years, then every 6 months for 3 years, then annually

Up to 10 years

Telephone follow-up

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• Pembrolizumab
• Ramucirumab

Trial Overview The trial tests combining Pembrolizumab (an immunotherapy), Ramucirumab (blocks blood vessel growth in tumors), and Docetaxel (a chemotherapy drug). It aims to see if this mix is safer and works better than the current standard care after NSCLC patients' disease progresses following specific prior treatments.

How Is the Trial Designed?

Group I: Treatment (docetaxel, ramucirumab, pembrolizumab) Experimental Treatment 3 Interventions

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.

Docetaxel is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in European Union as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a study of 237 patients with advanced non-small cell lung cancer (NSCLC), those who received prior immune checkpoint inhibitors (ICI) showed significantly better outcomes when treated with ramucirumab (RAM) and docetaxel (DOC), including higher objective response rates and longer progression-free survival (PFS).

The results suggest that RAM and DOC are more effective when administered after ICI treatment compared to other therapies like cytotoxic agents, bevacizumab, or tyrosine kinase inhibitors, especially in patients who had a favorable tumor response to prior ICI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequencing strategies with ramucirumab and docetaxel following prior treatments for advanced non-small cell lung cancer: a multicenter retrospective cohort study. Tanizaki, S., Matsumoto, K., Tamiya, A., et al.[2023]

In a study involving 25 patients with advanced non-small cell lung cancer and asymptomatic brain metastases, the combination of ramucirumab and docetaxel showed a median progression-free survival of 3.9 months and a median overall survival of 20.9 months, indicating potential efficacy for this patient group.

The treatment was generally well-tolerated, with no severe adverse events like intracranial hemorrhage reported, although 40% of patients experienced grade 3 or higher neutropenia, suggesting that while the combination is promising, further studies with larger sample sizes are necessary to fully assess safety and tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab Plus Docetaxel for Patients with Non-small cell Lung Cancer with Brain Metastases: A Multicenter, Open-Label Single-Arm Phase II Trial. Tanimura, K., Uchino, J., Kimura, H., et al.[2023]

Ramucirumab, when combined with docetaxel, improves overall survival by 1.4 months for patients with metastatic non-small cell lung cancer (NSCLC) who have progressed after platinum-based chemotherapy.

The treatment has an acceptable safety profile, but its role may be influenced by the introduction of PD-1-blocking antibodies like nivolumab or pembrolizumab in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab for the treatment of advanced or metastatic non-small cell lung cancer. Takeda, K., Daga, H.[2023]

Ramucirumab, approved by the FDA for treating metastatic non-small cell lung cancer (NSCLC), significantly improves overall survival when combined with docetaxel, showing a median survival of 10.5 months compared to 9.1 months with placebo in a study of 1,253 patients.

The treatment has an acceptable safety profile, with common side effects including fatigue, neutropenia, and diarrhea, although some patients experienced more severe reactions like febrile neutropenia and hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration Approval Summary: Ramucirumab for the Treatment of Metastatic Non-Small Cell Lung Cancer Following Disease Progression On or After Platinum-Based Chemotherapy. Larkins, E., Scepura, B., Blumenthal, GM., et al.[2023]

In a study of 99 patients with non-small cell lung cancer (NSCLC), the combination of docetaxel (DTX) and ramucirumab (Ram) significantly improved progression-free survival (PFS) in patients who had previously received anti-PD-1/L1 therapy, with a median PFS of 5.9 months compared to 2.8 months for DTX alone.

In patients who had not received anti-PD-1/L1 therapy, there was no significant difference in PFS or overall survival (OS) between those treated with DTX alone and those treated with DTX plus Ram, suggesting that Ram may specifically enhance DTX efficacy after prior immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of ramucirumab enhances docetaxel efficacy in patients who had received anti-PD-1/PD-L1 treatment. Tozuka, T., Kitazono, S., Sakamoto, H., et al.[2023]

In a study of 237 patients with previously treated non-small cell lung cancer (NSCLC), the combination of docetaxel and ramucirumab showed an overall response rate of 25.2% and a disease control rate of 63.9%, with a median progression-free survival of 4.5 months.

The study found that while lung and liver metastases responded well to treatment, patients with poor ECOG performance status (2 or more) and brain metastasis had significantly shorter progression-free survival, indicating that this combination therapy should be used cautiously in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of docetaxel plus ramucirumab on metastatic site in previously treated patients with non-small cell lung cancer: a multicenter retrospective study. Matsumoto, K., Tamiya, A., Matsuda, Y., et al.[2022]

In a phase II study involving 160 Japanese patients with non-small cell lung cancer (NSCLC), the combination of ramucirumab and docetaxel significantly prolonged progression-free survival (PFS) compared to placebo-docetaxel, with a median PFS of 5.22 months versus 4.21 months.

While overall survival rates were similar between the two groups, the ramucirumab-docetaxel combination showed a higher objective response rate (28.9% vs 18.5%) and a higher disease control rate (78.9% vs 70.4%), although it was associated with a higher incidence of febrile neutropenia (34.2% vs 19.8%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, phase II study of ramucirumab plus docetaxel vs placebo plus docetaxel in Japanese patients with stage IV non-small cell lung cancer after disease progression on platinum-based therapy. Yoh, K., Hosomi, Y., Kasahara, K., et al.[2023]

In a study of 114 patients with advanced non-small cell lung cancer, the combination of ramucirumab and docetaxel (RAM+DOC) showed similar efficacy in older patients (75 years and older) compared to younger patients, with median overall survival of 11.2 months for older patients versus 12.2 months for younger patients.

The safety profile of RAM+DOC was well tolerated in older patients, especially when combined with prophylactic pegylated-granulocyte-colony stimulating factor (PEG-G-CSF), suggesting that this treatment approach could be a viable option for older patients with advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of ramucirumab plus docetaxel in older patients with advanced non-small cell lung cancer. Sakaguchi, T., Furuya, N., Ito, K., et al.[2023]

In a study of 237 patients with advanced non-small cell lung cancer, the combination of Ramucirumab and Docetaxel showed similar overall survival rates in older patients (≥65 years) compared to younger patients (<65 years), indicating that this treatment can be effective across age groups.

However, older patients experienced a higher rate of severe adverse events (56.7% vs. 42.7% in younger patients), suggesting that careful monitoring and potential dose reduction of Docetaxel may enhance safety and improve survival outcomes in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ramucirumab plus docetaxel in older patients with advanced non-small cell lung cancer: A multicenter retrospective cohort study. Matsumoto, K., Tamiya, A., Inagaki, Y., et al.[2023]

In a study of 288 patients with advanced non-small cell lung cancer (NSCLC), extended treatment with immune checkpoint inhibitors (ICIs) for more than 180 days and maintenance therapy were identified as significant predictors of improved progression-free survival (PFS) and overall survival (OS) when transitioning to ramucirumab plus docetaxel (RD) as second-line therapy.

The analysis showed that factors like performance status and histology (specifically adenocarcinoma) also independently predicted better outcomes after RD treatment, while the therapeutic response and PD-L1 expression were not closely linked to the results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended ICI treatment after first-line chemoimmunotherapy could predict the clinical benefit of ramucirumab plus docetaxel in advanced non-small lung cancer: Post hoc analysis from NEJ051 (REACTIVE study). Yamaguchi, O., Mori, K., Takata, S., et al.[2023]

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02914-4/fulltext

1340P A phase II study of docetaxel (D), ramucirumab (R), ... The combination of docetaxel, ramucirumab and pembrolizumab was well tolerated and demonstrated activity that warrants further evaluation in pts with R/M NSCLC.

2. swog.org swog.org/news-events/news/2022/06/03/drug-combo-improved-survival-nsclc

Drug Combo Improved Survival in NSCLC Patients with advanced non-small cell lung cancer whose cancer had progressed on previous immunotherapy lived significantly longer when treated with a ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0169500225005252

Phase III study of ramucirumab plus docetaxel versus ... This study compared ramucirumab plus docetaxel with atezolizumab monotherapy in previously treated NSCLC patients.

4. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00480-7/fulltext

Efficacy and safety of second-line therapy of docetaxel plus ... Although docetaxel plus ramucirumab demonstrated a survival benefit over docetaxel after platinum-based chemotherapy for non-small cell lung ...

5. cancernetwork.com cancernetwork.com/view/pembrolizumab-plus-ramucirumab-yields-improved-survival-vs-soc-in-ici-resistant-nsclc

Pembrolizumab Plus Ramucirumab Yields Improved ... The combination of pembrolizumab plus ramucirumab resulted in better overall survival compared with the standard of care regimens despite similar response ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10507469/

Clinical outcomes of ramucirumab plus docetaxel in the ... In the REVEL trial, ramucirumab plus docetaxel demonstrated significant improvements in overall survival (OS), progression-free survival ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/PMC10507469

Clinical outcomes of ramucirumab plus docetaxel in the ... The safety profile across studies was consistent between both treatment groups, and no new safety signals were reported. Conclusions: ...