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

Phase 2

Completed

• Conditions: Resectable; Early-stage; NSCLC
• Interventions: Drug: Durvalumab; Combination Product: Oleclumab; Combination Product: Monalizumab; Combination Product: Danvatirsen

• Registration Number: NCT03794544
• Lead Sponsor: MedImmune LLC

Brief 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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-12-10
• Study First Submitted QC: 2019-01-02
• Study First Posted: 2019-01-07
• Study Start: 2019-03-08
• Primary Completion: 2021-01-13
• Study Completion: 2021-01-13
• Results First Submitted: 2022-01-11
• Status Verified: 2022-02
• Results First Submitted QC: 2022-02-23
• Last Update Submitted: 2022-02-23
• Results First Posted: 2022-02-24
• Last Update Posted: 2022-02-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 84

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Durvalumab 1500 mg + Oleclumab 3000 mg	Oleclumab	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).
Durvalumab 1500 mg + Monalizumab 750 mg	Monalizumab	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).
Durvalumab 1500 mg + Danvatirsen 200 mg	Danvatirsen	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).
Durvalumab 1500 mg	Durvalumab	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).
Durvalumab 1500 mg + Oleclumab 3000 mg	Durvalumab	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).
Durvalumab 1500 mg + Monalizumab 750 mg	Durvalumab	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).
Durvalumab 1500 mg + Danvatirsen 200 mg	Durvalumab	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).

Primary Outcome Measures

Name	Time	Method
Major Pathological Response Rate	Day 1 through Day 42	Major pathological response rate is defined as percentage of participants with \<=10% residual viable tumor cells in the resected specimen.

Secondary Outcome Measures

Name	Time	Method
Pathological Complete Response (pCR) Rate	Day 1 through Day 42	The pCR rate is defined as percentage of participants with no residual viable tumor cells in the resected specimen.
Feasibility to Surgery	Day 29 to Day 42 after Week 1 Day 1	Feasibility to surgery is defined as the percentage of participants who underwent the planned surgery within Days 29 to 42 after Week 1 Day 1.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	From Day 1 through Day 105	An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Number of Participants With Grade 3 or Grade 4 Clinical Laboratory Toxicities	From Day 1 through Day 105	Participants with Grade 3 or Grade 4 clinical laboratory toxicities are reported. Laboratory tests included hematology, coagulation, chemistry, and urinalysis.
Number of Participants With Abnormal Vital Signs Reported as TEAEs	From Day 1 through Day 105	Participants with abnormal vital sign reported as TEAEs are reported.

Trial Locations

Locations (1)

Research Site; 🇨🇭 Zurich, Switzerland