COMPEL: A Study to Evaluate Chemotherapy Plus Osimertinib Against Chemotherapy Plus Placebo in Patients With Non-small Cell Lung Cancer (NSCLC)

• Sponsor: AstraZeneca (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04765059
• Collaborator: Parexel (Industry)
• Enrollment: 204
• Locations: 44
• Arms: 2
• Anticipated Duration (Months): 39.6
• Patients Per Site: 4.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The study will evaluate the efficacy and safety of treatment with chemotherapy in combination with osimertinib compared to chemotherapy in combination with placebo in patients who have progressed extracranially following first-line osimertinib treatment.

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer	Drug: Osimertinib (AZD9291) pemetrexed cisplatin or carboplatin; Drug: Placebo for osimertinib (AZD9291) pemetrexed cisplatin or carboplatin	Phase 3

Detailed Description

This is a Phase III, randomized, double-blind, placebo-controlled study of platinum plus pemetrexed chemotherapy plus osimertinib versus platinum plus pemetrexed chemotherapy plus placebo in patients with epidermal growth factor receptor mutation-positive (EGFRm), metastatic NSCLC who responded to first-line osimertinib therapy and subsequently experienced radiological, extracranial disease progression. Approximately 204 patients will be randomized in a 1:1 ratio to treatment with platinum plus pemetrexed chemotherapy plus osimertinib (Treatment Arm A) or platinum plus pemetrexed chemotherapy plus placebo (Treatment Arm B). Patients will be stratified based on the presence of brain metastases (stable brain metastases based on central nervous system (CNS) Response Evaluation Criteria in Solid Tumors, Version 1.1 [RECIST 1.1] assessments versus no brain metastases).

The 2 randomized treatment regimens are as follows:

• Treatment Arm A: Osimertinib 80 mg once daily (QD) with pemetrexed (500 mg/m^{2) (with pre-treatment) plus either cisplatin (75 mg/m}2) or carboplatin (area under the concentration-time curve [AUC] 5), both administered on Day 1 of 21-day cycles for 4 cycles, followed by osimertinib 80 mg QD plus pemetrexed maintenance (500 mg/m^2) on Day 1 of 21-day cycles

• Treatment Arm B: Placebo QD with pemetrexed (500 mg/m^{2) (with pre-treatment) plus either cisplatin (75 mg/m}2) or carboplatin (AUC5), both administered on Day 1 of 21-day cycles for 4 cycles, followed by placebo QD plus pemetrexed maintenance (500 mg/m^2) on Day 1 of 21-day cycles.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 204 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: The patient, the Investigator, and the study site staff will be blinded to the study drug or placebo allocation. Patients may participate in the open label part of trial at the discretion of the investigator to receive osimertinib and continue any ongoing chemotherapy if intracranial progression is their first progression event.
• Primary Purpose: Treatment
• Official Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Platinum Plus Pemetrexed Chemotherapy Plus Osimertinib Versus Platinum Plus Pemetrexed Chemotherapy Plus Placebo in Patients With EGFRm, Locally Advanced or Metastatic NSCLC Who Have Progressed Extracranially Following First-Line Osimertinib Therapy (COMPEL)
• Actual Study Start Date: Sep 12, 2021
• Anticipated Primary Completion Date: Jun 12, 2024
• Anticipated Study Completion Date: Dec 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Arm A All randomized patients will receive osimertinib 80 mg QD with pemetrexed (500 mg/m^2) (with pre-treatment) plus either cisplatin (75 mg/m^2) or carboplatin ([AUC] 5), both administered on Day 1 of 21-day cycles for 4 cycles, followed by osimertinib 80 mg QD plus pemetrexed maintenance (500 mg/m^2) on Day 1 of 21-day cycles	Drug: Osimertinib (AZD9291) pemetrexed cisplatin or carboplatin; Randomized patients will receive oral dose of osimertinib with intravenous (IV) pemetrexed plus either IV cisplatin or IV carboplatin
Placebo Comparator: Treatment Arm B All randomized patients will receive placebo QD with pemetrexed (500 mg/m^2) (with pre-treatment) plus either cisplatin (75 mg/m^2) or carboplatin (AUC5), both administered on Day 1 of 21-day cycles for 4 cycles, followed by placebo QD plus pemetrexed maintenance (500 mg/m^2) on Day 1 of 21-day cycles	Drug: Placebo for osimertinib (AZD9291) pemetrexed cisplatin or carboplatin; Randomized patients will receive oral dose of placebo matching osimertinib with IV pemetrexed plus either IV cisplatin or IV carboplatin

Outcome Measures

Primary Outcome Measures

1. Progression free survival (PFS): time from randomization until progression (intracranial or extracranial, whichever occurs first) per RECIST 1.1 (for extracranial progression) and CNS RECIST 1.1 (for intracranial progression) [At Screening,every 6 weeks for the first 13 cycles (each cycle is 21 days),then every 12 weeks, relative to randomization,and upto intracranial or extracranial disease progression or end of survival follow-up,whichever comes first (approximately 3 years)]

   To compare the efficacy of chemotherapy plus osimertinib treatment relative to chemotherapy plus placebo based on PFS

Secondary Outcome Measures

1. Intracranial PFS is defined as time from randomization until intracranial progression per CNS RECIST 1.1 as assessed by the Investigator at local site or death due to any cause [At Screening,every 6 weeks for the first 13 cycles (each cycle is 21 days),then every 12 weeks, relative to randomization,and upto intracranial or extracranial disease progression or end of survival follow-up,whichever comes first (approximately 3 years)]

   To compare the efficacy of chemotherapy plus osimertinib treatment relative to chemotherapy plus placebo based on intracranial PFS in patients with baseline brain metastases and patients without baseline brain metastases

2. Extracranial PFS is defined as time from randomization until extracranial progression per RECIST 1.1 as assessed by the Investigator at local site or death due to any cause [At Screening,every 6 weeks for the first 13 cycles (each cycle is 21 days),then every 12 weeks, relative to randomization,and upto intracranial or extracranial disease progression or end of survival follow-up,whichever comes first (approximately 3 years)]

   To compare the efficacy of chemotherapy plus osimertinib treatment relative to chemotherapy plus placebo based on extracranial PFS

3. OS: the length of time from randomization until the date of death due to any cause [At Screening,every 6 weeks for the first 13 cycles (each cycle is 21 days),then every 12 weeks, relative to randomization,and upto intracranial or extracranial disease progression or end of survival follow-up,whichever comes first (approximately 3 years)]

   To compare the efficacy of chemotherapy plus osimertinib treatment relative to chemotherapy plus placebo based on OS

4. Number of patients with serious and non-serious adverse events [From screening through post progression survival follow-up (at least once every 12 weeks relative to randomization)]

   To assess the safety and tolerability of chemotherapy plus osimertinib treatment relative to chemotherapy plus placebo in patients with metastatic EGFRm NSCLC who have progressed extracranially on first line osimertinib treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 130 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol.

2. Pathologically confirmed non-squamous NSCLC.

3. Locally advanced (clinical stage IIIB or IIIC) or metastatic NSCLC (clinical stage IVA or IVB) or recurrent NSCLC), not amenable to curative surgery or radiotherapy.

4. Evidence of radiological extracranial disease progression following response with first-line osimertinib treatment but who have not received further, subsequent treatment.

5. World Health Organization performance status of 0 to 1 at screening with no clinically significant deterioration in the previous 2 weeks.

6. Life expectancy >12 weeks at Day 1.

7. At least 1 lesion, not previously irradiated.

8. Females must be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of child-bearing potential, or must have evidence of non-child-bearing potential by fulfilling criteria at screening.

9. Male patients must be willing to use barrier contraception

Exclusion Criteria:

1. Clinical or radiological evidence of CNS progression on first-line osimertinib.

2. Past medical history of ILD (interstitial lung disease)/pneumonitis, drug-induced ILD/pneumonitis, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD/pneumonitis.

3. Any evidence of severe or uncontrolled extracranial diseases.

4. Any of the following cardiac criteria:

1. Mean resting QTc >470 msec ii) Any clinically important abnormalities in rhythm, conduction, or morphology of resting electrocardiogram iii) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events

1. Any concurrent and/or other active malignancy that has required treatment within 2 years of first dose of investigational product (IP).

2. Any unresolved toxicities from prior extracranial therapy.

3. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of osimertinib.

4. More than 4 weeks elapsed since last dose of osimertinib by date of randomization.

5. Unable to tolerate osimertinib 80 mg first-line therapy.

6. Prior treatment with any systemic anti-cancer therapy.

7. Major surgery within 4 weeks of the first dose of IP.

8. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of IP.

9. Current use of medications or herbal supplements known to be strong inducers of cytochrome P450 (CYP) 3A4.

10. Participation in another clinical study with an IP other than first-line osimertinib.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Silver Spring	Maryland	United States	20910
2	Research Site	Boston	Massachusetts	United States	02114
3	Research Site	Boston	Massachusetts	United States	02215
4	Research Site	Minneapolis	Minnesota	United States	55407
5	Research Site	Graz		Austria	8036
6	Research Site	Klagenfurt		Austria	9020
7	Research Site	Linz		Austria	4020
8	Research Site	Beijing		China	100005
9	Research Site	Beijing		China	100142
10	Research Site	Hohhot		China	010017
11	Research Site	Shenyang		China	110001
12	Research Site	Tianjin		China	300060
13	Research Site	Zhengzhou City		China	450008
14	Research Site	Berlin		Germany	12351
15	Research Site	Hannover		Germany	30625
16	Research Site	Hessen		Germany	61231
17	Research Site	Karlsruhe		Germany	76137
18	Research Site	Köln		Germany	50937
19	Research Site	Köln		Germany	51109
20	Research Site	München		Germany	D-80336
21	Research Site	Ulm		Germany	89081
22	Research Site	Beer Sheva		Israel	84101
23	Research Site	Jerusalem		Israel	9103102
24	Research Site	Jerusalem		Israel	9112001
25	Research Site	Kfar Saba		Israel	4428164
26	Research Site	Petah Tikva		Israel	494142
27	Research Site	Tel Aviv		Israel	6423906
28	Research Site	Tel Hashomer		Israel	52621
29	Research Site	Firenze		Italy	50134
30	Research Site	Meldola		Italy	47014
31	Research Site	Messina		Italy	98158
32	Research Site	Napoli		Italy	80131
33	Research Site	Padova		Italy	35128
34	Research Site	Palermo		Italy	90146
35	Research Site	Roma		Italy	00168
36	Research Site	Terni		Italy	05100
37	Research Site	Verona		Italy	37124
38	Research Site	Alicante		Spain	03010
39	Research Site	León		Spain	24071
40	Research Site	Madrid		Spain	28040
41	Research Site	Oviedo		Spain	33011
42	Research Site	Palma de Mallorca		Spain	07010
43	Research Site	Sevilla		Spain	41013
44	Research Site	Valencia		Spain	46010

Sponsors and Collaborators

• AstraZeneca
• Parexel

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT04765059
• Other Study ID Numbers: D5162C00042
• First Posted: Feb 21, 2021
• Last Update Posted: Aug 9, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by AstraZeneca: Osimertinib; Platinum; Pemetrexed; Epidermal growth factor receptor mutation positive (EGFRm); Extracranial progression
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Cisplatin; Carboplatin; Pemetrexed; Osimertinib

Study Results

No Results Posted as of Aug 9, 2022