Randomized Phase III Trial of MEDI4736 (Durvalumab) as Concurrent and Consolidative Therapy or Consolidative Therapy Alone for Unresectable Stage 3 NSCLC

Plain English Summary

Testing the Addition of an Antibody to Standard Chemoradiation Followed by the Antibody for One Year to Standard Chemoradiation Followed by One Year of the Antibody in Patients With Unresectable Stage III Non-Small Cell Lung Cancer is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying Recurrent Lung Non-Small Cell Carcinoma, Stage III Lung Cancer AJCC v8, Stage IIIA Lung Cancer AJCC v8, Stage IIIB Lung Cancer AJCC v8, Stage IIIC Lung Cancer AJCC v8, Unresectable Lung Non-Small Cell Carcinoma. Tests if adding an antibody (durvalumab) to standard chemoradiation can improve survival and prevent tumor recurrence. For patients with unresectable stage III non-small cell lung cancer (NSCLC). Participation involves receiving chemotherapy, radiation, and durvalumab for up to a year. Alternative treatments include standard chemoradiation followed by durvalumab. The trial aims to enroll 660 participants.

Official Summary

This phase III trial studies how well an antibody (durvalumab) with chemotherapy and radiation therapy (chemoradiation) works in treating patients with stage III non-small cell lung cancer that cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This study is being done to see if adding durvalumab to standard chemoradiation followed by additional durvalumab can extend patients life and/or prevent the tumor from coming back compared to the usual approach of chemoradiation alone followed by durvalumab.

Who Can Participate

Here is what you need to know about eligibility for this trial. 18 years or older, confirmed stage IIIA/B/C NSCLC, good performance status, no recent weight loss, normal organ function, and no other cancers. Excludes pregnant women, those with recent chemotherapy or radiation, and those with certain other cancers. Age: 18+ years, Health: Good organ function, No: Recent chemotherapy, pregnancy, other cancers. This trial is studying Recurrent Lung Non-Small Cell Carcinoma, Stage III Lung Cancer AJCC v8, Stage IIIA Lung Cancer AJCC v8, Stage IIIB Lung Cancer AJCC v8, Stage IIIC Lung Cancer AJCC v8, Unresectable Lung Non-Small Cell Carcinoma, so participants generally need a confirmed diagnosis.

What They're Measuring

Measures survival and tumor response, which can mean longer life and fewer cancer returns for patients. The specific primary outcome measures are: Overall survival (OS) (From randomization to death from any cause, assessed up to 10 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to fill a gap in treatment options for stage III NSCLC by potentially improving survival and preventing recurrence. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Recurrent Lung Non-Small Cell Carcinoma, Stage III Lung Cancer AJCC v8, Stage IIIA Lung Cancer AJCC v8, Stage IIIB Lung Cancer AJCC v8, Stage IIIC Lung Cancer AJCC v8, Unresectable Lung Non-Small Cell Carcinoma, where improved treatment options are needed.

Investor Insight

Market size is large, with strong competition but a high approval probability due to unmet needs in NSCLC treatment. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 660 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor about your eligibility and potential side effects. Participation involves receiving chemotherapy, radiation, and durvalumab for up to a year. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 660 participants

Interventions

• DRUG: Carboplatin — Given IV
• DRUG: Cisplatin — Given IV
• BIOLOGICAL: Durvalumab — Given IV
• DRUG: Etoposide — Given IV
• DRUG: Paclitaxel — Given IV

Primary Outcomes

• Overall survival (OS) (From randomization to death from any cause, assessed up to 10 years)

Secondary Outcomes

• Progression-free survival (PFS) (From randomization to documented disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or death from any cause, whichever occurs first, assessed up to 10 years)
• Best objective response (Up to 10 years)
• Incidence of adverse events (Up to 10 years)
• Local progression (Up to 10 years)

Full Eligibility Criteria

Inclusion Criteria:

* STEP 1 INCLUSION ELIGIBILITY CRITERIA - CONCURRENT THERAPY
* Patient must be \>= 18 years old
* Patient must have one of the following:

  * Newly diagnosed stage IIIA/B/C non-small cell lung cancer (NSCLC) (per the American Joint Committee on Cancer \[AJCC\] 8th edition) that is unresectable and is histologically and/or cytologically confirmed
  * Nodal recurrence after surgery for early stage NSCLC
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Patient must have a body weight \> 30 kg
* Patient must not have unintentional weight loss \> 10% within 30 days prior to registration
* Patient must have a baseline electrocardiography (ECG) obtained within 6 weeks prior to registration
* Patient must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Baseline imaging assessments and measurements used to evaluate all measurable or non-measurable sites of disease must be done within 4 weeks prior to registration
* Absolute neutrophil count (ANC) \>= 1500 cells/uL (obtained =\< 7 days prior to registration)
* White blood cells (WBC) counts \>= 2500/uL (obtained =\< 7 days prior to registration)
* Platelet count \>= 100,000/uL (obtained =\< 7 days prior to registration)
* Hemoglobin \>= 9.0 g/dL (obtained =\< 7 days prior to registration)
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) with the following exception: patients with known Gilbert disease who have serum bilirubin level =\< 3 x ULN may be enrolled (obtained =\< 7 days prior to registration)
* Aspartate aminotransferase (AST) and alanine transaminase (ALT) =\< 3.0 x institutional ULN (obtained =\< 7 days prior to registration)
* Serum creatinine =\< 1.5 x institutional ULN or creatinine clearance \>= 45 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation (obtained =\< 7 days prior to registration)
* Patient must have pulmonary function tests (PFTs) with both forced expiratory volume in 1 second (FEV1) and diffusion capacity of the lung for carbon monoxide (DLCO) \>= 40% of predicted, obtained within 5 months prior to registration
* Patient is expected to have lung volume (V)20 of =\< 35%, after radiation oncologist views pre-treatment work up
* Patients with nodal recurrence after surgery for early-stage NSCLC are eligible if the following criteria are met:

  * No prior chemotherapy or radiation was ever administered for this lung cancer originally or for recurrence prior to entering this protocol
  * Prior curative-intent surgery was at least 90 days prior to the nodal recurrence
  * No prior radiation was administered to the region of study cancer that would cause overlap of treatment fields
* Patients who are human immunodeficiency virus (HIV) positive may participate in the study IF they meet all of the following eligibility requirements:

  * They must be stable on their anti-retroviral regimen, and they must be healthy from an HIV perspective
  * They must have a CD4 count of greater than 250 cells/mcL, obtained within 6 months prior to registration
  * They must not be receiving prophylactic therapy for an opportunistic infection
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Patients must not have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to registration
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used
* All patients of childbearing potential must have a negative blood test or urine study, with a minimum sensitivity 50 mlU/L or equivalent units of HCG, within 7 days prior to registration to rule out pregnancy. A patient of childbearing potential is anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patients must not expected to conceive or father children by using accepted and highly effective method(s) of contraception during sexual intercourse for at least one week prior to the start of treatment, during protocol treatment, and continue for 90 days after the last dose of protocol treatment.

  * Highly effective methods of contraception include Etonogestrel-releasing implants (Implanon or Norplant), Intravaginal: Ethinylestradiol/etonogestrel-releasing intravaginal devices: e.g., NuvaRing, injection: Medroxyprogeste

Trial Locations

• Anchorage Associates in Radiation Medicine, Anchorage, Alaska, United States
• Anchorage Radiation Therapy Center, Anchorage, Alaska, United States
• Alaska Breast Care and Surgery LLC, Anchorage, Alaska, United States
• Alaska Oncology and Hematology LLC, Anchorage, Alaska, United States
• Alaska Women's Cancer Care, Anchorage, Alaska, United States
• Anchorage Oncology Centre, Anchorage, Alaska, United States
• Katmai Oncology Group, Anchorage, Alaska, United States
• Providence Alaska Medical Center, Anchorage, Alaska, United States
• Fairbanks Memorial Hospital, Fairbanks, Alaska, United States
• Banner MD Anderson Cancer Center, Gilbert, Arizona, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Lung cancer, non-small cell lung cancer (NSCLC), stage III lung cancer, recurrent lung cancer, immunotherapy

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