A Study of Selpercatinib After Surgery or Radiation in Participants With Non-Small Cell Lung Cancer (NSCLC) (LIBRETTO-432)

Loxo Oncology

Status and phase: Enrolling; Phase 3

Conditions: Carcinoma, Non-Small-Cell Lung

Treatments: Drug: Placebo; Drug: Selpercatinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04819100

2023-506784-33-00 (Other Identifier)

2020-005191-35 (EudraCT Number)

J2G-MC-JZJX (Other Identifier)

18126

Details and patient eligibility

About

The reason for this study is to see if the study drug, selpercatinib, compared to placebo is effective and safe in delaying cancer return in participants with early-stage non-small cell lung cancer (NSCLC), who have already had surgery or radiation. Participants who are assigned to placebo and stop the study drug because their disease comes back or gets worse have the option to potentially crossover to selpercatinib. Participation could last up to three years.

Enrollment: 170 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Must have histologically confirmed Stage IB, II, or IIIA NSCLC.

• Must have an activating RET gene fusion in tumor based on polymerase chain reaction (PCR), next generation sequencing (NGS), or another molecular test per sponsor's approval.

• Must have received definitive locoregional therapy with curative intent (surgery or radiotherapy) for Stage IB, II, or IIIA NSCLC.

  -- Must have undergone the available anti-cancer therapy (including chemotherapy or durvalumab) or not be suitable for it, based on the investigator's discretion.

• Maximum time allowed between definitive therapy completion and randomization must be:

  • 10 weeks if no chemotherapy was administered
  • 26 weeks if adjuvant chemotherapy was administered

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

• Adequate hematologic, hepatic, and renal function.

• Willingness of men and women of reproductive potential to observe conventional and highly effective birth control for the duration of the study and for at least 2 weeks after last dose of study drug.

Exclusion criteria

• Additional oncogenic drivers in NSCLC, if known.
• Evidence of small cell lung cancer.
• Clinical or radiologic evidence of disease recurrence or progression following definitive therapy.
• Known or suspected interstitial fibrosis or interstitial lung disease or history of (noninfectious) pneumonitis that required steroids.
• Clinically significant active cardiovascular disease or history of myocardial infarction within six months prior to planned start of selpercatinib or prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF) greater than 470 milliseconds.
• Have known uncontrolled human immunodeficiency virus (HIV)-1/2 infection.
• Have known active hepatitis B or C.
• Active uncontrolled systemic bacterial, viral, or fungal infection or serious ongoing intercurrent illness, such as hypertension or diabetes, despite optimal treatment.
• Major surgery within 4 weeks prior to planned start of selpercatinib.
• Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug.
• Other malignancy unless nonmelanoma skin cancer, carcinoma in situ of the cervix or other in situ cancers or a malignancy diagnosed greater than or equal to two years previously and not currently active.
• Pregnancy or lactation.
• Prior treatment with a selective RET inhibitor (e.g. selpercatinib or pralsetinib).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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170 participants in 2 patient groups, including a placebo group

Selpercatinib

Experimental group

Description:

Selpercatinib administered orally.

Treatment:

Drug: Selpercatinib

Placebo

Placebo Comparator group

Description:

Placebo administered orally.

Treatment:

Drug: Placebo