Combination Chemotherapy and Immunotherapy for Non-Small Cell Lung Cancer

(NeoCOAST-2 Trial)

Recruiting in Palo Alto (17 mi)

+69 other locations

Overseen by Tina Cascone

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: AstraZeneca

Must not be taking: Immunosuppressants, Chemotherapy, Biologics, others

Disqualifiers: EGFR mutations, ALK translocations, Autoimmune disorders, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The study is intended to assess the safety and efficacy of perioperative treatment with Durvalumab in combination with Oleclumab, Monalizumab, or AZD0171 and platinum doublet chemotherapy (CTX); or Volrustomig or Rilvegostomig in combination with CTX; or Datopotamab deruxtecan (Dato-DXd) in combination with Durvalumab or Rilvegostomig and single agent platinum chemotherapy in participants with resectable, early-stage non-small cell lung cancer.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but you cannot use immunosuppressive medication within 14 days before starting the study. It's best to discuss your current medications with the trial team.

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

Research shows that combining pemetrexed with platinum-based drugs like cisplatin or carboplatin improves survival in non-small cell lung cancer patients. Additionally, adding pembrolizumab, an immunotherapy drug, to this combination further enhances survival rates, regardless of specific tumor characteristics. ^{1 2 3 4 5}

Is the combination of chemotherapy and immunotherapy for non-small cell lung cancer safe?

The combination of pemetrexed with cisplatin or carboplatin has been studied for safety in non-small cell lung cancer patients. Common side effects include fatigue, nausea, and blood-related issues like neutropenia (low white blood cell count). Some serious side effects, such as skin reactions, have been reported, but taking vitamins and steroids can help reduce these risks. ^{1 6 7 8 9}

How is the combination chemotherapy and immunotherapy treatment for non-small cell lung cancer different from other treatments?

This treatment is unique because it combines chemotherapy, which directly kills cancer cells, with immunotherapy, which helps the immune system fight cancer. This dual approach may offer a more comprehensive attack on the cancer compared to traditional chemotherapy alone. ^{1 10 11 12 13}

Research Team

Tina Cascone

Principal Investigator

MD Anderson Cancer Center Houston, TX 77030

Eligibility Criteria

This trial is for newly diagnosed NSCLC patients with resectable disease stages IIA-IIIB, who have good organ and bone marrow function, can provide recent tumor samples to check certain biomarkers, and have a performance status of 0 or 1. It excludes those with autoimmune disorders, prior cancer treatments, planned lung surgeries like pneumonectomy, EGFR mutations/ALK translocations, heart issues including QTcF ≥470 ms, previous immune therapy or specific ADCs use.

Inclusion Criteria

I am fully active or can carry out light work.

My organs and bone marrow are working well.

I can provide recent (≤ 6 months old) tumor samples for PD-L1, EGFR, or ALK status testing.

Exclusion Criteria

I do not have any active or uncontrolled infections.

I am scheduled for radiotherapy before surgery as part of my treatment plan.

I am not currently on any cancer treatments like chemotherapy or hormone therapy.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive neoadjuvant treatment with various combinations of Durvalumab, Oleclumab, Monalizumab, Volrustomig, Rilvegostomig, AZD0171, Dato-DXd, and chemotherapy

6-8 weeks

Surgery

Participants undergo surgical resection of the tumor

1 week

Adjuvant Treatment

Participants receive adjuvant treatment with various combinations of Durvalumab, Oleclumab, Monalizumab, Volrustomig, Rilvegostomig, AZD0171, and Dato-DXd

12-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Carboplatin (Chemotherapy)
• Cisplatin (Chemotherapy)
• Dato-DXd (Antibody-Drug Conjugate)
• Durvalumab (Monoclonal Antibodies)
• MEDI5752 (Monoclonal Antibodies)
• Monalizumab (Monoclonal Antibodies)
• Oleclumab (Monoclonal Antibodies)
• Paclitaxel (Chemotherapy)
• Pemetrexed (Chemotherapy)

Trial Overview The study tests the safety and effectiveness of perioperative treatment combining Durvalumab with Oleclumab/Monalizumab/AZD0171 plus platinum-based chemo; MEDI5752 plus platinum chemo; or Dato-DXd with Durvalumab and single-agent platinum chemo in early-stage NSCLC that can be surgically removed.

Participant Groups

Group I: Arm 7: Dato-DXd + Rilvegostomig + single agent platinum Experimental Treatment 4 Interventions

Participants will receive Dato-DXd + Rilvegostomig + single agent platinum as neoadjuvant treatment and Rilvegostomig as adjuvant treatment. Participants will receive one of the following chemotherapy regimens, based on physician choice of as part of their treatment regimen prior to surgery: Carboplatin or Cisplatin

Group II: Arm 6: Rilvegostomig + CTX Experimental Treatment 4 Interventions

Participants will receive Rilvegostomig + CTX as neoadjuvant treatment and Rilvegostomig as adjuvant treatment. Participants will receive one of the following chemotherapy regimens, based on the tumour histology and Investigator's discretion, as part of their treatment regimen prior to surgery: Carboplatin/Paclitaxel Pemetrexed/Cisplatin Pemetrexed/Carboplatin

Group III: Arm 5: AZD0171 + durvalumab + CTX Experimental Treatment 5 Interventions

Participants will receive AZD0171 + durvalumab + CTX as neoadjuvant treatment and AZD0171 + durvalumab as adjuvant treatment. Participants will receive one of the following chemotherapy regimens, based on the tumour histology and Investigator's discretion, as part of their treatment regimen prior to surgery: Carboplatin/Paclitaxel Pemetrexed/Cisplatin Pemetrexed/Carboplatin

Group IV: Arm 4: Dato-DXd + durvalumab + single agent platinum Experimental Treatment 4 Interventions

Participants will receive Dato-DXd + durvalumab + single agent platinum as neoadjuvant treatment and durvalumab as adjuvant treatment. Participants will receive one of the following chemotherapy regimens, based on physician choice of as part of their treatment regimen prior to surgery: Carboplatin or Cisplatin

Group V: Arm 3: Volrustomig (Dose Exploration) + CTX Experimental Treatment 4 Interventions

Participants will receive Volrustomig + CTX as neoadjuvant treatment and Volrustomig as adjuvant treatment. Participants will receive one of the following chemotherapy regimens, based on the tumour histology and Investigator's discretion, as part of their treatment regimen prior to surgery: Carboplatin/Paclitaxel Pemetrexed/Cisplatin Pemetrexed/Carboplatin

Group VI: Arm 2: Monalizumab + Durvalumab + CTX Experimental Treatment 5 Interventions

Participants will receive Durvalumab + Monalizumab + CTX as neoadjuvant treatment and Durvalumab + Monalizumab as adjuvant treatment. Participants will receive one of the following chemotherapy regimens, based on the tumour histology and Investigator's discretion, as part of their treatment regimen prior to surgery: Carboplatin/Paclitaxel Pemetrexed/Cisplatin Pemetrexed/Carboplatin

Group VII: Arm 1: Oleclumab + Durvalumab + Platinum doublet chemotherapy (CTX) Experimental Treatment 5 Interventions

Participants will receive Durvalumab + Oleclumab + CTX as neoadjuvant treatment and Durvalumab + Oleclumab as adjuvant treatment. Participants will receive one of the following chemotherapy regimens, based on the tumour histology and Investigator's discretion, as part of their treatment regimen prior to surgery: Carboplatin/Paclitaxel Pemetrexed/Cisplatin Pemetrexed/Carboplatin

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Research Site Omaha, NE

Research Site Buffalo, NY

Research Site Memphis, TN

Research Site Seattle, WA

More Trial Locations

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4491

Patients Recruited

290,540,000+

Parexel

Industry Sponsor

Trials

322

Patients Recruited

137,000+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed plus cisplatin/carboplatin in previously treated locally advanced or metastatic non-small cell lung cancer patients. Zhang, GZ., Jiao, SC., Meng, ZT.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed plus platinum with or without pembrolizumab in patients with previously untreated metastatic nonsquamous NSCLC: protocol-specified final analysis from KEYNOTE-189. Rodríguez-Abreu, D., Powell, SF., Hochmair, MJ., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined Checkpoint Inhibition and Chemotherapy: New Era of 1st-Line Treatment for Non-Small-Cell Lung Cancer. Wang, C., Kulkarni, P., Salgia, R.[2020]

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]

In the KEYNOTE-189 study, first-line treatment with pembrolizumab combined with pemetrexed-platinum significantly improved overall survival (OS) to a median of 22.0 months compared to 10.7 months for the placebo group, indicating a strong efficacy in treating metastatic nonsquamous non-small-cell lung cancer (NSCLC).

The combination therapy also resulted in a median progression-free survival (PFS) of 9.0 months versus 4.9 months for placebo, with benefits observed regardless of tumor PD-L1 expression or the presence of liver/brain metastases, while maintaining a similar incidence of serious adverse events between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non-Small-Cell Lung Cancer. Gadgeel, S., Rodríguez-Abreu, D., Speranza, G., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed and carboplatin combination therapy followed by pemetrexed maintenance in Japanese patients with non-squamous non-small cell lung cancer: A subgroup analysis of elderly patients. Nogami, N., Nishio, M., Okamoto, I., et al.[2022]

In a study involving 361 patients with advanced nonsquamous non-small-cell lung cancer, the combination of pemetrexed and carboplatin (Pem+Cb) did not show a significant advantage in progression-free survival without grade 4 toxicity compared to paclitaxel, carboplatin, and bevacizumab (Pac+Cb+Bev).

While both treatment regimens were generally well tolerated, Pem+Cb was associated with higher rates of grade 3/4 anemia and thrombocytopenia, whereas Pac+Cb+Bev had more cases of grade 3/4 neutropenia and alopecia, indicating differing toxicity profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients ith advanced nonsquamous non-small-cell lung cancer. Zinner, RG., Obasaju, CK., Spigel, DR., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxic epidermal necrolysis after pemetrexed and cisplatin for non-small cell lung cancer in a patient with sharp syndrome. Then, C., von Einem, JC., Müller, D., et al.[2015]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase II study of pemetrexed in combination with cisplatin or carboplatin as first-line therapy for patients with locally advanced or metastatic non-small-cell lung cancer. Schuette, WH., Gröschel, A., Sebastian, M., et al.[2022]

NCBI (Pubmed)

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. Yadav, A., Malik, PS., Khurana, S., et al.[2021]

Pemetrexed, when combined with carboplatin, has shown promising antitumor activity with mild toxicity in phase II clinical trials, but it can lead to serious adverse reactions such as toxic epidermal necrolysis, as seen in a reported case.

Supplementation with folic acid and vitamin B12 is recommended during pemetrexed treatment to help reduce the risk of hematological and gastrointestinal side effects, although severe skin reactions can still occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxic epidermal necrolysis related to pemetrexed and carboplatin with vitamin B12 and folic acid supplementation for advanced non-small cell lung cancer. Bosch-Barrera, J., Gaztañaga, M., Ceballos, J., et al.[2015]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase III Study of Docetaxel Plus Cisplatin Versus Pemetrexed Plus Cisplatin as First-line Treatment of Nonsquamous Non-Small-cell Lung Cancer: A TRAIL Trial. Park, CK., Oh, IJ., Kim, KS., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Pemetrexed plus cisplatin/carboplatin in previously treated locally advanced or metastatic non-small cell lung cancer patients. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Pemetrexed plus platinum with or without pembrolizumab in patients with previously untreated metastatic nonsquamous NSCLC: protocol-specified final analysis from KEYNOTE-189. [2022]

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

Combined Checkpoint Inhibition and Chemotherapy: New Era of 1st-Line Treatment for Non-Small-Cell Lung Cancer. [2020]

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

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

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

Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non-Small-Cell Lung Cancer. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Pemetrexed and carboplatin combination therapy followed by pemetrexed maintenance in Japanese patients with non-squamous non-small cell lung cancer: A subgroup analysis of elderly patients. [2022]

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

PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients ith advanced nonsquamous non-small-cell lung cancer. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Toxic epidermal necrolysis after pemetrexed and cisplatin for non-small cell lung cancer in a patient with sharp syndrome. [2015]

9. England pubmed.ncbi.nlm.nih.gov

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

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

A randomized phase II study of pemetrexed in combination with cisplatin or carboplatin as first-line therapy for patients with locally advanced or metastatic non-small-cell lung cancer. [2022]

11. 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]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Toxic epidermal necrolysis related to pemetrexed and carboplatin with vitamin B12 and folic acid supplementation for advanced non-small cell lung cancer. [2015]

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

Randomized Phase III Study of Docetaxel Plus Cisplatin Versus Pemetrexed Plus Cisplatin as First-line Treatment of Nonsquamous Non-Small-cell Lung Cancer: A TRAIL Trial. [2018]