Chemo/Immunotherapy for Non-Small Cell Lung Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Thomas Lycan

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Wake Forest University Health Sciences

Must not be taking: Immunosuppressive drugs

Disqualifiers: Autoimmune disease, Pneumonitis, Cardiac illness, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This pilot study is configured as a non-inferiority comparison of Performance Status 2 patients with Performance Status 0-1 patients, with the goal of demonstrating non-inferiority in terms of efficacy (progression-free survival, overall survival) and safety (rates of adverse events, quality of life) when treating Performance Status 2 patients with the same first-line immunotherapy-based regimen as Performance Status 0-1 patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on medications for an active autoimmune disease or have a history of pneumonitis requiring treatment, you may not be eligible to participate.

What data supports the effectiveness of this drug combination for non-small cell lung cancer?

Research shows that combining pembrolizumab with chemotherapy drugs like carboplatin and pemetrexed is effective for treating advanced non-small cell lung cancer. Studies have found this combination to be promising, with real-world use supporting its effectiveness. ^{1 2 3 4 5}

Is the combination of chemo/immunotherapy for non-small cell lung cancer generally safe?

The combination of pembrolizumab with chemotherapy, including drugs like pemetrexed and carboplatin, has been studied for safety in non-small cell lung cancer. Common side effects include neutropenia (low white blood cell count), fatigue, nausea, and vomiting, but these treatments are generally considered safe with proper monitoring and supportive care. ^{1 2 6 7 8}

How is the chemo/immunotherapy treatment for non-small cell lung cancer unique?

This treatment combines chemotherapy drugs like carboplatin, nab-paclitaxel, and paclitaxel with the immunotherapy drug pembrolizumab, which helps the immune system fight cancer cells. It is unique because it integrates both chemotherapy and immunotherapy, offering a comprehensive approach that is now a standard first-line treatment for advanced non-small cell lung cancer. ^{1 4 9 10 11}

Research Team

Thomas Lycan

Principal Investigator

Wake Forest University Health Sciences

Eligibility Criteria

This trial is for adults with non-small cell lung cancer that's metastatic or can't be surgically removed, and who haven't had chemo or immunotherapy before. They should have a life expectancy over 3 months, normal organ/marrow function, and no history of certain conditions like pneumonitis treated with steroids.

Inclusion Criteria

I am 18 years old or older.

My blood tests show normal white blood cell and platelet counts.

I haven't had chemotherapy or immunotherapy for my cancer, except possibly for early-stage treatment.

Exclusion Criteria

I have an autoimmune disease treated within the last 2 years.

I have had lung inflammation treated with steroids.

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab every 3 weeks, with additional chemotherapy drugs based on subtype and biomarker status, for 4 cycles

12 weeks

4 visits (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Carboplatin (Platinum-containing Compounds)
• Nab paclitaxel (Alkylating agents)
• Paclitaxel (Plant Alkaloids)
• Pembrolizumab (Monoclonal Antibodies)
• Pemetrexed (Antimetabolites)

Trial Overview The study tests if patients with lower performance status (weaker condition) do as well on first-line immunotherapy-based treatments as those in better condition. It involves drugs like Pembrolizumab and chemotherapy agents, along with quality of life assessments.

Participant Groups

Group I: Performance Status 2 Participants Experimental Treatment 8 Interventions

ALL study participants will receive pembrolizumab 200 mg intravenously (IV) on day 1 of each 3-week cycle. Participants with predictive biomarker PD-L1 greater than or equal to 50%: Participants will not receive any other drugs besides pembrolizumab. Participants with Non-squamous subtype, predictive biomarker (PD-L1 less than 50%): Participants will ALSO receive: - Carboplatin area under the curve (AUC) 5 IV on day 1 of each 3-week cycle for 4 cycles. PLUS - Pemetrexed 500 mg/m2 IV on day 1 of each 3-week cycle for 4 cycles. Participants with Squamous subtype, predictive biomarker (PD-L1 less than 50%): Participants will also receive: * Carboplatin AUC 5 IV on day 1 of each 3-week cycle for 4 cycles. PLUS * Paclitaxel 200 mg/m2 IV on day 1 of each 3-week cycle for 4 cycles. OR * Nab-paclitaxel 100 mg/m2 on day 1, 8, 15 of 3-week cycle for 4 cycles

Group II: Performance Status 0-1 Participants Experimental Treatment 8 Interventions

ALL study participants will receive pembrolizumab 200 mg intravenously (IV) on day 1 of each 3-week cycle. Participants with predictive biomarker PD-L1 greater than or equal to 50%: Participants will not receive any other drugs besides pembrolizumab. Participants with Non-squamous subtype, predictive biomarker (PD-L1 less than 50%): Participants will ALSO receive: - Carboplatin area under the curve (AUC) 5 IV on day 1 of each 3-week cycle for 4 cycles. PLUS - Pemetrexed 500 mg/m2 IV on day 1 of each 3-week cycle for 4 cycles. Participants with Squamous subtype, predictive biomarker (PD-L1 less than 50%): Participants will also receive: * Carboplatin AUC 5 IV on day 1 of each 3-week cycle for 4 cycles. PLUS * Paclitaxel 200 mg/m2 IV on day 1 of each 3-week cycle for 4 cycles. OR * Nab-paclitaxel 100 mg/m2 on day 1, 8, 15 of 3-week cycle for 4 cycles

Carboplatin is already approved in Canada for the following indications:

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Dr. L. Ebony Boulware

Wake Forest University Health Sciences

Chief Medical Officer since 2022

MD from Duke University School of Medicine, MPH from Johns Hopkins Bloomberg School of Public Health

Dr. Julie Ann Freischlag

Wake Forest University Health Sciences

Chief Executive Officer since 2020

BS from University of Illinois, MD from Rush University

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). Renaud, E., Ricordel, C., Corre, R., et al.[2023]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a real-world study of 54 patients with advanced non-squamous non-small cell lung cancer, the combination of carboplatin, pemetrexed, and pembrolizumab showed a higher disease control rate (86.7%) compared to carboplatin and pemetrexed alone (54%).

Patients with brain metastases treated with the combination therapy had a significantly lower progression rate (33.3%) compared to those receiving only carboplatin and pemetrexed (91.7%), indicating that this regimen may be particularly effective for this challenging patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A tertiary care cancer center experience with carboplatin and pemetrexed in combination with pembrolizumab in comparison with carboplatin and pemetrexed alone in non-squamous non-small cell lung cancer. Afzal, MZ., Dragnev, K., Shirai, K.[2023]

Pemetrexed (Alimta) shows a response rate of 16%-23% as a single agent for non-small-cell lung cancer (NSCLC) and a higher response rate of 38.9%-44.8% when combined with cisplatin, leading to a median survival of 8.9-10.9 months.

The main side effect of pemetrexed is neutropenia, but this can be mitigated with vitamin B12 and folate supplements, highlighting the importance of supportive care in enhancing treatment safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed (Alimta): a new antifolate for non-small-cell lung cancer. Ettinger, DS.[2017]

Pemetrexed, when combined with cisplatin, significantly improves median survival in patients with malignant pleural mesothelioma, with a median survival of 12.1 months compared to 9.3 months for cisplatin alone, based on a phase III trial involving 448 patients.

The drug works by inhibiting key enzymes involved in DNA synthesis, but it can cause side effects like myelosuppression, neutropenia, and fatigue, necessitating supportive care with folic acid, vitamin B12, and corticosteroids during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA drug approval summaries: pemetrexed (Alimta). Hazarika, M., White, RM., Johnson, JR., et al.[2022]

In a study involving 812 patients with malignant pleural mesothelioma (MPM), single-agent pemetrexed showed promising efficacy, with a median time to progressive disease of 6.0 months for chemonaïve patients and an overall response rate of 10.5%.

The treatment was well-tolerated, exhibiting mild hematologic toxicity, primarily neutropenia, in less than 18% of patients, indicating a favorable safety profile for pemetrexed in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-agent pemetrexed for chemonaïve and pretreated patients with malignant pleural mesothelioma: results of an International Expanded Access Program. Taylor, P., Castagneto, B., Dark, G., et al.[2015]

The phase 3 IMpower132 study demonstrated that the combination of atezolizumab with carboplatin or cisplatin plus pemetrexed (APP) significantly improved progression-free survival (PFS) in patients with stage IV nonsquamous NSCLC, with a median PFS of 7.6 months compared to 5.2 months for the standard chemotherapy (PP).

While overall survival (OS) showed a numerical improvement for the APP group (median OS of 17.5 months vs. 13.6 months for PP), this difference was not statistically significant, indicating that APP has a manageable safety profile with no new safety concerns, although it did have a higher incidence of grade 3 or 4 adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab Plus Chemotherapy for First-Line Treatment of Nonsquamous NSCLC: Results From the Randomized Phase 3 IMpower132 Trial. Nishio, M., Barlesi, F., West, H., et al.[2021]

The combination of carboplatin and dose-dense pemetrexed with involved field radiotherapy is feasible for treating locally advanced and oligometastatic non-small cell lung cancer (NSCLC), as shown in a phase I study with 18 enrolled patients.

Despite some dose-limiting toxicities observed, the treatment resulted in a median survival time of 28.6 months, with 13 out of 16 evaluable patients showing a local regional response, indicating promising efficacy for this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase i study of 'dose-dense' pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma. Shen, X., Denittis, A., Werner-Wasik, M., et al.[2021]

The ANTELOPE trial is a phase II study comparing the efficacy of a pemetrexed-free regimen (atezolizumab, carboplatin, and nab-paclitaxel) against a pemetrexed-based regimen (pembrolizumab, cis-/carboplatin, and pemetrexed) in treating TTF-1 negative non-small cell lung adenocarcinoma (NSCLC/ADC).

This trial aims to enroll 136 participants across 30 sites in Germany, focusing on overall survival as the primary endpoint, which will help determine the best treatment approach for this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and Design of the Phase II ANTELOPE Study of Atezolizumab, Carboplatin and nab-Paclitaxel vs. Pembrolizumab, Platinum and Pemetrexed in TTF-1 Negative, Metastatic Lung Adenocarcinoma (AIO-TRK-0122). Frost, N., Bleckmann, A., Griesinger, F., et al.[2023]

References

1. China pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). [2023]

2. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

3. China pubmed.ncbi.nlm.nih.gov

A tertiary care cancer center experience with carboplatin and pemetrexed in combination with pembrolizumab in comparison with carboplatin and pemetrexed alone in non-squamous non-small cell lung cancer. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

An Open-Label Randomized Controlled Trial Comparing the Efficacy and Safety of Pemetrexed-Carboplatin versus (Weekly) Paclitaxel-Carboplatin as First-Line Chemotherapy in Advanced Non-Squamous Non-Small Cell Lung Cancer. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Pemetrexed (Alimta): a new antifolate for non-small-cell lung cancer. [2017]

6. England pubmed.ncbi.nlm.nih.gov

FDA drug approval summaries: pemetrexed (Alimta). [2022]

7. Spain pubmed.ncbi.nlm.nih.gov

Pemetrexed disodium for the treatment of NSCLC: an update. [2017]

8. United States pubmed.ncbi.nlm.nih.gov

Single-agent pemetrexed for chemonaïve and pretreated patients with malignant pleural mesothelioma: results of an International Expanded Access Program. [2015]

9. United States pubmed.ncbi.nlm.nih.gov

Atezolizumab Plus Chemotherapy for First-Line Treatment of Nonsquamous NSCLC: Results From the Randomized Phase 3 IMpower132 Trial. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Phase i study of 'dose-dense' pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Rationale and Design of the Phase II ANTELOPE Study of Atezolizumab, Carboplatin and nab-Paclitaxel vs. Pembrolizumab, Platinum and Pemetrexed in TTF-1 Negative, Metastatic Lung Adenocarcinoma (AIO-TRK-0122). [2023]