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

NSCLC Clinical Trial

Official title:

A Phase 2 Open-label, Multicenter, Randomized, Multidrug Platform Study of Neoadjuvant Durvalumab Alone or in Combination With Novel Agents in Subjects With Resectable, Early-stage (I [> 2 cm] to IIIA) Non-small Cell Lung Cancer (NeoCOAST)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03794544
• Other study ID #: D9108C00002
• Status: Completed
• Phase: Phase 2
• Start date: March 8, 2019
• Est. completion date: January 13, 2021

Study information

• Verified date: February 2022
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: January 13, 2021
• Est. primary completion date: January 13, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 102 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Early-stage
• Lung Neoplasms
• NSCLC
• Resectable

Intervention

Drug:
• Durvalumab
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.

Combination Product:
• Oleclumab
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
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
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.

Locations

Country	Name	City	State
Canada	Research Site	Montreal	Quebec
France	Research Site	Marseille Cedex 9
France	Research Site	Toulouse CEDEX 09
Italy	Research Site	Orbassano
Portugal	Research Site	Porto
Spain	Research Site	A Coruña
Spain	Research Site	Barcelona
Switzerland	Research Site	Zurich
United States	Research Site	Baltimore	Maryland
United States	Research Site	Buffalo	New York
United States	Research Site	Chattanooga	Tennessee
United States	Research Site	Fairfax	Virginia
United States	Research Site	Fort Myers	Florida
United States	Research Site	Houston	Texas
United States	Research Site	La Jolla	California
United States	Research Site	Leesburg	Florida
United States	Research Site	Nashville	Tennessee
United States	Research Site	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Countries where clinical trial is conducted

United States,  Canada,  France,  Italy,  Portugal,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major Pathological Response Rate	Major pathological response rate is defined as percentage of participants with <=10% residual viable tumor cells in the resected specimen.	Day 1 through Day 42
Secondary	Pathological Complete Response (pCR) Rate	The pCR rate is defined as percentage of participants with no residual viable tumor cells in the resected specimen.	Day 1 through Day 42
Secondary	Feasibility to Surgery	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.	Day 29 to Day 42 after Week 1 Day 1
Secondary	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	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.	From Day 1 through Day 105
Secondary	Number of Participants With Grade 3 or Grade 4 Clinical Laboratory Toxicities	Participants with Grade 3 or Grade 4 clinical laboratory toxicities are reported. Laboratory tests included hematology, coagulation, chemistry, and urinalysis.	From Day 1 through Day 105
Secondary	Number of Participants With Abnormal Vital Signs Reported as TEAEs	Participants with abnormal vital sign reported as TEAEs are reported.	From Day 1 through Day 105

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