A Study to Evaluate the Safety and Efficacy of Selinexor With or Without Pembrolizumab Versus Standard of Care in Previously Treated Metastatic Colorectal Cancer With RAS Mutations

NCT04854434 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: XPORT-CRC-041
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of selinexor alone or with pembrolizumab in participants with advanced or metastatic colorectal cancer (CRC). Approximately 78 participants with advanced or metastatic CRC will be enrolled, and randomized (1:1:1) into three arms A (selinexor only), B (selinexor and pembrolizumab), and C (standard of care \[Combination of trifluridine and tipiracil\]). Randomization will be based on stratification factors: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 versus 2. The end of treatment (EoT) visit will occur less than or equal to (\<=30) days post-treatment discontinuation. A survival follow-up visit will be performed every 3 months from EoT and will continue for 12 months.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Arm B and C: Progression-free Survival (PFS) as Assessed by the Investigator Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

  PFS was defined as the time from the date of randomization until disease progression or death due to any cause, whichever occurs first. PFS was assessed by the investigator per RECIST 1.1. As per RECIST 1.1 criteria, PD was defined as at least a 20% increase in the sum of the longest diameter (SLD), taking as reference the smallest sum of the longest diameter (SLD) recorded from baseline or the appearance of 1 or more new lesions.

  From the date of randomization until disease progression or death, whichever occurs first (up to 8 months)

Secondary Outcomes (11)

• Arm A, B and C: Overall Survival (OS)

  From the date of randomization up to death (up to 8 months)

• Arm B and C: Overall Response Rate (ORR)

  From the date of randomization until the documentation of CR or PR, whichever occurs first (up to 8 months)

• Arm A and C: Overall Response Rate (ORR)

  From the date of randomization until the documentation of CR or PR, whichever occurs first (up to 8 months)

• Arm A, B and C: Progression-free Survival (PFS) at 6 Months

  At 6 Months

• Arm A, B and C: Percentage of Participants With Overall Survival (OS) at 6 Months

  At 6 Months

Study Arms (3)

Arm A: Selinexor 80 mg

EXPERIMENTAL

Participants received a single dose of selinexor 80 mg (4 tablets of 20 mg) orally QW on Day 1 of each week of a 42-day cycle (i.e., on Days 1, 8, 15, 22, 29, and 36 of each 42-day cycle) until PD, intolerable toxicity, or withdrawal from the study (maximum exposure: 33 weeks).

Drug: Selinexor

Arm B: Selinexor 80 mg and Pembrolizumab 400 mg

EXPERIMENTAL

Participants received a single dose of selinexor 80 mg (4 tablets of 20 mg) orally QW on Day 1 of each week of a 42-day cycle (i.e., on Days 1, 8, 15, 22, 29, and 36 of each 42-day cycle) in combination with pembrolizumab 400 mg IV once every 6 weeks of each 42-day cycle until PD, intolerable toxicity, or withdrawal from the study (maximum exposure: 30 weeks).

Drug: Selinexor; Drug: Pembrolizumab

Arm C: Standard of care (SOC)

ACTIVE COMPARATOR

Participants received combination of trifluridine and tipiracil 35 mg/m\^2/dose tablets orally BID (maximum 80 mg per dose) as SOC on Days 1 through 5 and Days 8 through 12 of each 28-day cycle until PD, intolerable toxicity, or withdrawal from the study (maximum exposure: 11 weeks).

Drug: Trifluridine; Drug: Tipiracil

Interventions

Selinexor DRUG

Participants will receive selinexor oral tablets.

Also known as: Xpovio, KPT-330

Arm A: Selinexor 80 mg; Arm B: Selinexor 80 mg and Pembrolizumab 400 mg

Pembrolizumab DRUG

Participants will receive pembrolizumab intravenously.

Also known as: Keytruda

Arm B: Selinexor 80 mg and Pembrolizumab 400 mg

Trifluridine DRUG

Participants will receive trifluridine oral tablets as SOC.

Arm C: Standard of care (SOC)

Tipiracil DRUG

Participants will receive tipiracil oral tablets as SOC.

Arm C: Standard of care (SOC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants have histologically proven diagnosis of unresectable metastatic colorectal cancer with a known rat sarcoma (RAS) mutation.
• Participants have measurable disease according to RECIST 1.1 criteria.
• Have received 2-3 prior lines of systemic anticancer treatment (adjuvant or neoadjuvant therapy is not counted as one line of systemic therapy).
• Participants with stable previously treated brain metastases are allowed.
• ECOG performance status of 0-2 at the time of screening.
• Age ≥ 18 years at the time of signing informed consent
• Life expectancy of at least 3 months.
• Female participants of childbearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male participants must use an effective barrier method of contraception if sexually active throughout the study and for 4 months after the last dose of selinexor or pembrolizumab or 6 months after trifluridine and tipiracil.
• Written informed consent signed in accordance with federal, local, and institutional guidelines.

You may not qualify if:

• Prior treatment with a selective inhibitor of nuclear export (SINE) compound or selinexor.
• Prior treatment with immune checkpoint inhibitors.
• Participants with microsatellite instability high (MSI-H) or deficient mismatch repair (dMMR).
• Known allergy to any of study drugs (selinexor, pembrolizumab, and trifluridine and tipiracil) or the excipient of pembrolizumab.
• Significant cardiovascular impairment, defined as:
• Left ventricular ejection fraction ≤ 40 percent (%)
• Active congestive heart failure (New York Heart Association \[NYHA\]) Class ≥ 3
• Unstable angina or myocardial infarction within 3 months of enrollment
• Serious and potentially life-threatening arrhythmia
• Absolute neutrophil count (ANC) less than (\<) 1500/cubic millimeter (mm\^3)
• Platelet count \< 100,000/ mm\^3
• Hemoglobin (Hb) \< 10 gram per deciliter (g/dL)
• Significant renal impairment, defined as: calculated creatinine clearance (CrCl) of \< 30 milliliter per minute (mL/min) using the formula of Cockcroft and Gault.
• Impaired hepatic function defined as: total bilirubin greater than (\>) 1.5 × upper limit of normal (ULN) and aspartate transaminase (AST) \> 2.5 x ULN, AST \> 2.5 x ULN; for Arm B, unless bilirubin elevation is related to Gilbert's Syndrome for which bilirubin must be ≤ 4 x ULN.
• Participants with a diagnosis of immunodeficiency or are receiving systemic steroid therapy (\>10 mg/day of prednisone or equivalent) or any other form of immunosuppressive therapy. Participants with active autoimmune disease requiring systemic treatment during the past 2 years.

Sponsors & Collaborators

• Karyopharm Therapeutics Inc: lead

Study Sites (3)

Valkyrie Clinical Trials

Los Angeles, California, 90067, United States

Location

Christiana Care Health Services, Christiana Hospital

Newark, Delaware, 19718, United States

Location

BRCR Global

Plantation, Florida, 33322, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

selinexor; pembrolizumab; Trifluridine; tipiracil

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

Prior to study completion, the signal was assessed by sponsor to be uncompetitive in the current treatment landscape and thus CRC program was closed. Thereby some of the protocol planned analysis were not performed and thus no data was reported for those outcome measures.

Results Point of Contact

• Title: Karyopharm Medical Information
• Organization: Karyopharm Therapeutics Inc

clinicaltrials@karyopharm.com

(888) 209-9326

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2021
• First Posted: April 22, 2021
• Study Start: June 29, 2021
• Primary Completion: June 24, 2022
• Study Completion: June 24, 2022
• Last Updated: November 3, 2023
• Results First Posted: November 3, 2023

Record last verified: 2023-10

Locations

US (3)