Pembrolizumab with Lenvatinib versus Docetaxel for Metastatic NSCLC after Platinum Doublet Chemotherapy and Immunotherapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

26 Jun 2019 → 23 Aug 2024

Decision date (initial)

2023-07-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC · Eisai Limited, UK

External identifiers

EU CT number

2022-501439-18-00

EudraCT number

2018-003791-12

WHO UTN

U1111-1280-4337

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Safety, Pharmacogenetic, Pharmacokinetic, Therapy, Efficacy

1. To compare pembrolizumab (MK-3475) + lenvatinib (MK-7902) to docetaxel with respect to overall survival (OS)
2. To compare pembrolizumab + lenvatinib to docetaxel with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR)

Secondary objectives 7

1. To compare pembrolizumab (MK-3475) + lenvatinib (MK-7902) to docetaxel with respect to objective response rate (ORR) per RECIST 1.1 by BICR.
2. To compare pembrolizumab + lenvatinib to lenvatinib monotherapy with respect to ORR per RECIST 1.1 by BICR.
3. To assess duration of response (DOR) with pembrolizumab + lenvatinib and docetaxel per RECIST 1.1 by BICR
4. To assess the safety and tolerability of treatment with pembrolizumab + lenvatinib versus docetaxel
5. To assess the safety and tolerability of treatment with lenvatinib monotherapy
6. To compare pembrolizumab + lenvatinib to docetaxel with respect to the mean change from baseline in global health status/quality of life (QoL), cough, chest pain, dyspnea, and physical functioning
7. To compare pembrolizumab + lenvatinib to docetaxel with respect to time to true deterioration (TTD) in global health status/QoL, cough, chest pain, dyspnea, and physical functioning scales

Conditions and MedDRA coding

NSCLC with squamous or nonsquamous histology

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Has a histologically or cytologically confirmed diagnosis of metastatic squamous or nonsquamous NSCLC (Stage IV: M1a, M1b, M1c).
2. Has PD on treatment with one prior anti-PD-1/PD-L1 monoclonal antibody (mAb) administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies. Retreatment with the same anti-PD-L1/PD-L1 mAb is acceptable in the overall course of treatment.
3. Has PD during/after platinum doublet chemotherapy for metastatic disease.
4. Has confirmation that EGFR-, ALK-, or ROS1-directed therapy is not indicated as primary therapy (documentation of absence of tumor-activating EGFR mutations [eg, DEL19 or L858R], and absence of ALK and ROS1 gene rearrangements OR presence of a K-ras mutation).
5. Has submitted pre-study imaging that confirmed evidence of PD following initiation of an anti-PD-1/PD-L1 inhibitor.
6. Has at least 1 measurable lesion by computerized tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1, as determined by the local site assessment.
7. Has provided tumor tissue for PD-L1 biomarker analysis from an archival sample (defined as: from initial diagnosis of NSCLC and prior to receiving immunotherapy [antiPD-1/PD-L1], from the primary lesion or a metastatic lesion).
8. Has provided prior to allocation tissue from a newly obtained formalin-fixed sample from a new biopsy (defined as: after completion of immunotherapy [anti-PD-1/PD-L1] and before receiving a randomization number), of a tumor lesion not previously irradiated.
9. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days before the first dose of study intervention but before randomization.
10. Has a life expectancy of at least 3 months
11. Male participants receiving pembrolizumab ± lenvatinib or lenvatinib must agree to refrain from donating sperm, and either 1) be abstinent from heterosexual intercourse; or 2) follow contraceptive guidance during the treatment period or 7 days after the last dose of lenvatinib. Male participants receiving docetaxel agree to adhere to the same conditions during the treatment period and for ≥90 days after the last dose of study treatment. Contraceptive use should either follow the study requirements or the local regulations for the study interventions, whichever is more stringent.
12. Female participants must not be pregnant, not be breastfeeding, and not be a woman of child-bearing potential (WOCBP). If a WOCBP, agrees to not donate eggs and either use contraception, or be abstinent from heterosexual intercourse during the treatment period and for ≥120 days after the last dose of pembrolizumab or 30 days after the last dose of lenvatinib, whichever occurs last. If a WOCBP receiving docetaxel, agrees to adhere to the same conditions during the treatment period and for ≥30 days after the last dose of study treatment. Contraception use should either follow the study requirements or the local regulations for the study interventions, whichever is more stringent.
13. Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mm Hg and no change in antihypertensive medications within 1 week before randomization
14. If participant received major surgery or radiation therapy of >30 Gy, they have recovered from the toxicity and/or complications from the intervention.
15. Has adequate organ function.

Exclusion criteria 24

1. Has received docetaxel as monotherapy or in combination with other therapies.
2. Has received lenvatinib as monotherapy or in combination with an anti-PD-1/PD-L1 mAb.
3. Has received: 1) radiotherapy within 2 weeks before the first dose of study treatment; or 2) lung radiation therapy >30 Gy within 6 months before the first dose of study treatment.
4. Has received a live vaccine within 30 days before the first dose of study treatment.
5. Has clinically significant hemoptysis or tumor bleeding within 2 weeks before the first dose of study treatment.
6. Has radiographic evidence of intratumoral cavitation, encasement, or invasion of a major blood vessel.
7. Has clinically significant cardiovascular impairment within 12 months of the first dose of study treatment.
8. Has a history of a gastrointestinal condition or procedure that may affect oral absorption of study treatment.
9. Has a pre-existing ≥Grade 3 gastrointestinal or non-gastrointestinal fistula.
10. Is currently participating in a clinical trial and receiving study therapy or participated in a study of an investigational agent within 4 weeks of the first dose of study treatment.
11. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of study treatment.
12. Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of disease recurrence for 3 years since initiation of that therapy.
13. Has known active central nervous system metastases and/or carcinomatous meningitis.
14. Has severe hypersensitivity to pembrolizumab and/or any of its excipients.
15. Has a sensitivity to any of the excipients contained in lenvatinib and/or docetaxel.
16. Has an active autoimmune disease that has required systemic treatment in the past 2 years.
17. Has a history of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.
18. Has an active infection requiring systemic therapy.
19. Has a known history of human immunodeficiency virus (HIV) infection.
20. Has a known history of hepatitis B reactive or known active hepatitis C virus infection.
21. Has active tuberculosis.
22. Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
23. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through at least 120 days after the last dose of pembrolizumab or lenvatinib, or 90 days (male participants) or 30 days (for female participants) after the last dose of docetaxel.
24. Has had an allogeneic tissue/solid organ transplant.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Overall Survival (OS)
2. Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

Secondary endpoints 15

1. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+Lenvatinib vs. Docetaxel
2. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+Lenvatinib vs. Lenvatinib Monotherapy
3. Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
4. Number of Participants Experiencing an Adverse Event (AE)
5. Number of Participants Discontinuing Study Treatment Due to an Adverse Event (AE)
6. Change from Baseline in European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status / Quality of Life (Items 29 & 30) Scale Combined Score
7. Change from Baseline in EORTC Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 31) Scale Score
8. Change from Baseline in EORTC QLQ-LC13 Chest Pain (Item 40) Scale Score
9. Change from Baseline in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score
10. Change from Baseline in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Combined Score
11. Time to True Deterioration (TTD) in EORTC QLQ-C30 Global Health Status / Quality of Life (Items 29 & 30) Scale Combined Score
12. Time to True Deterioration (TTD) in EORTC QLQ-LC13 Cough (Item 31) Scale Score
13. Time to True Deterioration (TTD) in EORTC QLQ-LC13 Chest Pain (Item 40) Scale Score
14. Time to True Deterioration (TTD) in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score
15. Time to True Deterioration (TTD) in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Combined Score

Investigational products

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

Test 3

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Debra Kush

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Debra Kush

Third parties 8

Locations

7 EU/EEA countries · 38 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 9 files

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

Application history

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