A Randomized Phase 3 Study of Sitravatinib in Combination with Nivolumab Versus Docetaxel in Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer with Disease Progression On or After Platinum-Based Chemotherapy and Checkpoint Inhibitor Therapy (SAPPHIRE)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Mirati Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

18 Dec 2020 → 1 Oct 2025

Decision date (initial)

2024-09-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Mirati Therapeutics, Inc.

External identifiers

EU CT number

2024-516598-60-00

EudraCT number

2019-001043-41

ClinicalTrials.gov

NCT03906071

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Pharmacokinetic, Safety

To compare Overall Survival (OS) in patients with non-squamous NSCLC who have experienced disease progression on or after platinum-based chemotherapy and CIT, treated with sitravatinib and nivolumab versus docetaxel.

Secondary objectives 5

1. To evaluate the safety of sitravatinib in combination with nivolumab in the study population.
2. To evaluate the relative tolerability of sitravatinib and nivolumab versus docetaxel.
3. To evaluate secondary efficacy endpoints in the study population.
4. To evaluate the pharmacokinetics (PK) of sitravatinib (MGCD516) administered in combination with nivolumab.
5. To evaluate health-related quality of life and lung cancer-specific symptoms in the study population.

Conditions and MedDRA coding

Advanced Non-Squamous Non-Small Cell Lung Cancer

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Diagnosis of Non-Squamous Non-Small Cell Lung Cancer
2. Receipt of at least one but not more than two prior treatment regimens in the advanced setting
3. Prior treatment with PD-1/PD-L1 checkpoint inhibitor therapy and platinum-based chemotherapy in combination or in sequence (i.e., platinum-based chemotheraphy followed by checkpoint inhibitor therapy)
4. Most recent treatment regimen must have included a checkpoint inhibitor therapy with radiographic disease progression on or after treatment
5. Candidate to receive docetaxel as second or third line therapy

Exclusion criteria 5

1. Uncontrolled brain metastases
2. Tumors that have tested positive for EGFR, ROS1, ALK mutations, or ALK fusions
3. Unacceptable toxicity with prior checkpoint inhibitor therapy
4. Receipt of systemic anti-cancer therapy post checkpoint inhibitor therapy, other than maintenance chemotherapy
5. Impaired heart function

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall Survival (OS)

Secondary endpoints 4

1. Safety characterized by type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events, laboratory abnormalities, and number of patients discontinuing study treatment due to an adverse event.
2. Secondary efficacy endpoints: - Objective Response Rate (ORR) as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). - Duration of Response (DOR); - Clinical Benefit Rate (CBR); - Progression-Free Survival (PFS); and - 1-Year Survival Rate.
3. Blood plasma concentrations of MGCD516.
4. Patient reported outcome (PROs): - Lung Cancer Symptom Scale (LCSS); and - European Quality of Life Five Dimensions Questionnaire (EQ-5D-5L).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Mirati Therapeutics Inc.

Sponsor organisation

Mirati Therapeutics Inc.

Address

Route 206, Province Line Road Province Line Road

City

Princeton

Postcode

08543

Country

United States

Scientific contact point

Organisation

Mirati Therapeutics Inc.

Contact name

Mirati Therapeutics, Inc.

Public contact point

Organisation

Mirati Therapeutics Inc.

Contact name

Mirati Therapeutics, Inc.

Third parties 11

Locations

3 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 23 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications