Neoadjuvant Durvalumab Alone or in Combination With Novel Agents in Resectable Non-Small Cell Lung Cancer
Condition: Resectable; Early-stage; NSCLC
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Durvalumab; Oleclumab; Monalizumab; Danvatirsen
Intervention description: Durvalumab 1500 mg IV will be administered Q4W (on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period.; Oleclumab 3000 mg IV will be administered Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period.; Monalizumab 750 mg IV will be administered Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period.; Danvatirsen 200 mg IV will be administered on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period) and later every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period.
Intervention MeSH terms: Durvalumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants will be enrolled and randomized into a durvalumab monotherapy arm or into a durvalumab plus other novel therapy arms. Up to approximately 25 sites globally will participate in this study. New treatment arms may be added in the future. Participants will be treated with a single durvalumab dose alone or in combination with other agents. After the single cycle treatment period participants will have the standard surgical resection planned. All participants will have a post-resection monitoring visit. Study treatment will be discontinued upon disease progression, unacceptable toxicity, or other investigators' reasons.
Masking: None (Open Label)
Enrollment: 84.0
Sex: All
Minimum age: 18 Years
Maximum age: 102 Years
Healthy volunteers: No
Keywords: Neoadjuvant; Non-small Cell Lung Cancer; Cancer; Lung; Resectable; Early-stage; Stage I; Stage II; Stage IIIA; Durvalumab

Summary:

      Study D9108C00002 (NeoCOAST) is a platform study assessing the effectiveness and safety of
      neoadjuvant durvalumab alone or in combination with novel agents in participants with
      resectable, early-stage (Stage I [>2cm] to IIIA) non-small cell lung cancer (NSCLC).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Cytologically and/or histologically-documented NSCLC

               1. Stage I (> 2 cm) to IIIA (for participants with N2 disease, only those with 1
                  single nodal station ≤ 3 cm are eligible) NSCLC according to the 8th edition of
                  American Joint Committee on Cancer staging classification

               2. Amenable to complete surgical resection

               3. Have not received any other therapy for this condition

          2. Predicted forced expiratory volume in one second (FEV1) ≥ 50%

          3. Predicted diffusing capacity of the lungs for carbon monoxide (DLCO) ≥ 50%

          4. ECOG 0 or 1

          5. Adequate organ function

        Exclusion Criteria:

          1. Participants with small-cell lung cancer or mixed small-cell lung cancer

          2. Participants who require or may require pneumonectomy

          3. Prior treatment with programmed cell death ligand-1 (PD-L1), PD-L1, or cytotoxic
             T-lymphocyte antigen 4 (CTLA-4) inhibitors

          4. Current or prior use of immunosuppressive medication within 14 days before the first
             dose of study drug.

          5. Active or prior documented autoimmune or inflammatory disorders. The following are
             exceptions to this criterion:

               1. Participants with vitiligo or alopecia

               2. Participants with hypothyroidism on hormone replacement

               3. Any chronic skin condition that does not require systemic therapy

               4. Participants without active disease in the last 5 years may be included but only
                  after consultation with the study physician

               5. Participants with celiac disease controlled by diet alone

          6. Pregnant or breast-feeding female

          7. Major surgical procedure within prior 30 days

          8. History of active primary immunodeficiency

          9. Active infection including tuberculosis, hepatitis B, hepatitis C, or HIV

         10. QTc interval (QTc) ≥ 470 ms

         11. Uncontrolled intercurrent illness that would limit compliance with study requirement,
             substantially increase risk of incurring AEs or compromise the ability of the
             participant to give written informed consent

         12. Receipt of live attenuated vaccination within 30 days prior to study entry

         13. History of another primary malignancy except for:

               1. Curative-treated malignancy with no known active disease > 2 years before
                  enrollment on the study

               2. Curative-treated non-melanoma skin cancer and/or carcinoma in-situ