Neoadjuvant Durvalumab Alone or in Combination With Novel Agents in Resectable Non-Small Cell Lung Cancer

MedImmune

Status and phase: Completed; Phase 2

Conditions: Resectable; Early-stage; NSCLC

Treatments: Combination Product: Monalizumab; Combination Product: Danvatirsen; Combination Product: Oleclumab; Drug: Durvalumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03794544

D9108C00002

Details and patient eligibility

About

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).

Enrollment: 84 patients

Sex: All

Ages: 18 to 102 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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84 participants in 4 patient groups

Durvalumab 1500 mg

Experimental group

Description:

Participants will receive durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection will be planned between Day 29 and Day 42. After surgical resection, participants will be followed up to Day 105 (starting from Week 1 Day 1).

Treatment:

Drug: Durvalumab

Durvalumab 1500 mg + Oleclumab 3000 mg

Experimental group

Description:

Participants will receive durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (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. Surgical resection will be planned between Day 29 and Day 42. After surgical resection, participants will be followed up to Day 105 (starting from Week 1 Day 1).

Treatment:

Drug: Durvalumab

Combination Product: Oleclumab

Durvalumab 1500 mg + Monalizumab 750 mg

Experimental group

Description:

Participants will receive durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV 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. Surgical resection will be planned between Day 29 and Day 42. After surgical resection, participants will be followed up to Day 105 (starting from Week 1 Day 1).

Treatment:

Drug: Durvalumab

Combination Product: Monalizumab

Durvalumab 1500 mg + Danvatirsen 200 mg

Experimental group

Description:

Participants will receive danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV 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. Surgical resection will be planned between Day 29 and Day 42. After surgical resection, participants will be followed up to Day 105 (starting from Week 1 Day 1).

Treatment:

Drug: Durvalumab

Combination Product: Danvatirsen