Open-Label, Dose-Escalation Study of Pemigatinib in Subjects With Advanced Malignancies - (FIGHT-101)

NCT ID: NCT02393248

Last Updated: 2023-01-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 201 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-27
• Study Completion Date: 2021-12-17

Brief Summary

The purpose of this study will be to evaluate the safety, tolerability, and pharmacological activity of pemigatinib in subjects with advanced malignancies. This study will have three parts, dose escalation (Part 1), dose expansion (Part 2) and combination therapy (Part 3).

Conditions

Lung Cancer; Solid Tumor; Gastric Cancer; Urothelial Cancer; Endometrial Cancer; Multiple Myeloma; Myeloproliferative Neoplasms; Breast Cancer; Cholangiocarcinoma; UC; MPN

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: Intermittent pemigatinib 1/2/4 mg QD

Participants self-administered oral pemigatinib 1/2/4 milligrams (mg) once daily (QD) on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break.

Group Type: EXPERIMENTAL

Pemigatinib

Intervention Type: DRUG

Part 1: Intermittent pemigatinib 6 mg QD

Participants self-administered oral pemigatinib 6 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break.

Group Type: EXPERIMENTAL

Pemigatinib

Intervention Type: DRUG

Part 1: Intermittent pemigatinib 9 mg QD

Participants self-administered oral pemigatinib 9 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break.

Group Type: EXPERIMENTAL

Pemigatinib

Intervention Type: DRUG

Part 1: Intermittent pemigatinib 13.5 mg QD

Participants self-administered oral pemigatinib 13.5 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break.

Group Type: EXPERIMENTAL

Pemigatinib

Intervention Type: DRUG

Part 1: Intermittent pemigatinib 20 mg QD

Participants self-administered oral pemigatinib 20 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break.

Group Type: EXPERIMENTAL

Pemigatinib

Intervention Type: DRUG

Part 1: Continuous pemigatinib 9 mg QD

Participants self-administered oral pemigatinib 9 mg QD on Days 1 through 21 of each 21-day cycle.

Group Type: EXPERIMENTAL

Pemigatinib

Intervention Type: DRUG

Part 1: Continuous pemigatinib 13.5 mg QD

Participants self-administered oral pemigatinib 13.5 mg QD on Days 1 through 21 of each 21-day cycle.

Group Type: EXPERIMENTAL

Pemigatinib

Intervention Type: DRUG

Part 1: Continuous pemigatinib 20 mg QD

Participants self-administered oral pemigatinib 20 mg QD on Days 1 through 21 of each 21-day cycle.

Group Type: EXPERIMENTAL

Pemigatinib

Intervention Type: DRUG

Part 1: Continuous pemigatinib 7.5 mg BID

Participants self-administered oral pemigatinib 7.5 mg twice daily (BID) on Days 1 through 21 of each 21-day cycle.

Group Type: EXPERIMENTAL

Pemigatinib

Intervention Type: DRUG

Part 1: Continuous pemigatinib 10 mg BID

Participants self-administered oral pemigatinib 10 mg BID on Days 1 through 21 of each 21-day cycle.

Group Type: EXPERIMENTAL

Pemigatinib

Intervention Type: DRUG

Part 2: Intermittent pemigatinib 9 mg QD

Participants self-administered oral pemigatinib 9 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break.

Group Type: EXPERIMENTAL

Pemigatinib

Intervention Type: DRUG

Part 2: Intermittent pemigatinib 13.5 mg QD

Participants self-administered oral pemigatinib 13.5 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break.

Group Type: EXPERIMENTAL

Pemigatinib

Intervention Type: DRUG

Part 2: Continuous pemigatinib 9 mg QD

Participants self-administered oral pemigatinib 9 mg QD on Days 1 through 21 of each 21-day cycle.

Group Type: EXPERIMENTAL

Pemigatinib

Intervention Type: DRUG

Part 2: Continuous pemigatinib 13.5 mg QD

Participants self-administered oral pemigatinib 13.5 mg QD on Days 1 through 21 of each 21-day cycle.

Group Type: EXPERIMENTAL

Pemigatinib

Intervention Type: DRUG

Part 2: Continuous pemigatinib 20 mg QD

Participants self-administered oral pemigatinib 20 mg QD on Days 1 through 21 of each 21-day cycle.

Group Type: EXPERIMENTAL

Pemigatinib

Intervention Type: DRUG

Part 3: Gem/Cis/intermittent pemigatinib 9 mg

Participants received gemcitabine (Gem) intravenously starting at 1000 mg/meters squared (m\^2) (30 minutes) on Days 1 and 8 of each 21-day cycle. Cisplatin (Cis) was administered intravenously starting at 70 mg/m\^2 (1-4 hours) once every 3 weeks on Day 1 of each 21-day cycle. Both gemcitabine and cisplatin doses could have been adjusted for toxicity management per commercial labeling. The investigator could have interrupted, modified, or discontinued chemotherapy with medical monitor approval. Participants self-administered oral pemigatinib 9 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. It was permissible to continue pemigatinib administration during the toxicity break of gemcitabine/cisplatin.

Group Type: EXPERIMENTAL

Pemigatinib

Intervention Type: DRUG

Gemcitabine

Intervention Type: DRUG

Cisplatin

Intervention Type: DRUG

Part 3: Gem/Cis/intermittent pemigatinib 13.5 mg

Participants received gemcitabine intravenously starting at 1000 mg/m\^2 (30 minutes) on Days 1 and 8 of each 21-day cycle. Cisplatin was administered intravenously starting at 70 mg/m\^2 (1-4 hours) once every 3 weeks on Day 1 of each 21-day cycle. Both gemcitabine and cisplatin doses could have been adjusted for toxicity management per commercial labeling. The investigator could have interrupted, modified, or discontinued chemotherapy with medical monitor approval. Participants self-administered oral pemigatinib 13.5 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. It was permissible to continue pemigatinib administration during the toxicity break of gemcitabine/cisplatin.

Group Type: EXPERIMENTAL

Pemigatinib

Intervention Type: DRUG

Gemcitabine

Intervention Type: DRUG

Cisplatin

Intervention Type: DRUG

Part 3: Tras/intermittent pemigatinib 13.5 mg

Trastuzumab (Tras) was administered as an open-label, commercial product at an initial dose of 8 mg/kilograms (kg) over a 90-minute intravenous infusion, followed by 6 mg/kg over a 30- to 90-minute intravenous infusion once every 3 weeks. The dose could have been adjusted for toxicity management, per commercial labeling. The investigator could have interrupted, modified, or discontinued trastuzumab with medical monitor approval. Participants self-administered oral pemigatinib 13.5 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. It was permissible to continue pemigatinib administration during the toxicity break of trastuzumab.

Group Type: EXPERIMENTAL

Pemigatinib

Intervention Type: DRUG

Trastuzumab

Intervention Type: DRUG

Part 3: Doc/intermittent pemigatinib 13.5 mg

Participants received docetaxel (Doc) intravenously starting at 75 mg/m\^2 (1 hour) once every 3 weeks on Day 1 of each cycle. The dose could have been adjusted for toxicity management per commercial labeling. The investigator could have interrupted, modified, or discontinued chemotherapy with medical monitor approval. Participants self-administered oral pemigatinib 13.5 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. It was permissible to continue pemigatinib administration during the toxicity break of docetaxel.

Group Type: EXPERIMENTAL

Pemigatinib

Intervention Type: DRUG

Docetaxel

Intervention Type: DRUG

Part 3: Pem/intermittent pemigatinib 9 mg

Participants received pembrolizumab (Pem) intravenously at 200 mg (30 minutes) once every 3 weeks on Day 1 of each cycle. The dose could have been adjusted for toxicity management per commercial labeling. The investigator could have interrupted, modified, or discontinued pembrolizumab with medical monitor approval. Participants self-administered oral pemigatinib 9 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. It was permissible to continue pemigatinib administration during the toxicity break of pembrolizumab.

Group Type: EXPERIMENTAL

Pemigatinib

Intervention Type: DRUG

Pembrolizumab

Intervention Type: DRUG

Part 3: Pem/intermittent pemigatinib 13.5 mg

Participants received pembrolizumab intravenously at 200 mg (30 minutes) once every 3 weeks on Day 1 of each cycle. The dose could have been adjusted for toxicity management per commercial labeling. The investigator could have interrupted, modified, or discontinued pembrolizumab with medical monitor approval. Participants self-administered oral pemigatinib 13.5 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. It was permissible to continue pemigatinib administration during the toxicity break of pembrolizumab.

Group Type: EXPERIMENTAL

Pemigatinib

Intervention Type: DRUG

Pembrolizumab

Intervention Type: DRUG

Part 3: Pem/continuous pemigatinib 13.5 mg

Participants received pembrolizumab intravenously at 200 mg (30 minutes) once every 3 weeks on Day 1 of each cycle. The dose could have been adjusted for toxicity management per commercial labeling. The investigator could have interrupted, modified, or discontinued pembrolizumab with medical monitor approval. Participants self-administered oral pemigatinib 13.5 mg QD on Days 1 through 21 of each 21-day cycle. It was permissible to continue pemigatinib administration during the toxicity break of pembrolizumab.

Group Type: EXPERIMENTAL

Pemigatinib

Intervention Type: DRUG

Pembrolizumab

Intervention Type: DRUG

Part 3: Ref/continuous pemigatinib 9 mg

Retifanlimab (Ref) was administered once every 4 weeks on a 28-day cycle as an open-label product, at an initial dose of 500 mg over a 60-minute intravenous infusion. Participants self-administered oral pemigatinib 9 mg QD on Days 1 through 21 of each 21-day cycle.

Group Type: EXPERIMENTAL

Pemigatinib

Intervention Type: DRUG

Retifanlimab

Intervention Type: DRUG

Part 3: Ref/continuous pemigatinib 13.5 mg

Retifanlimab was administered once every 4 weeks on a 28-day cycle as an open-label product, at an initial dose of 500 mg over a 60-minute intravenous infusion. Participants self-administered oral pemigatinib 13.5 mg QD on Days 1 through 21 of each 21-day cycle.

Group Type: EXPERIMENTAL

Pemigatinib

Intervention Type: DRUG

Retifanlimab

Intervention Type: DRUG

Part 3: Ref/continuous pemigatinib 20 mg

Retifanlimab was administered once every 4 weeks on a 28-day cycle as an open-label product, at an initial dose of 500 mg over a 60-minute intravenous infusion. Participants self-administered oral pemigatinib 20 mg QD on Days 1 through 21 of each 21-day cycle.

Group Type: EXPERIMENTAL

Pemigatinib

Intervention Type: DRUG

Retifanlimab

Intervention Type: DRUG

Interventions

Pemigatinib

Intervention Type: DRUG

Gemcitabine

Intervention Type: DRUG

Pembrolizumab

Intervention Type: DRUG

Docetaxel

Intervention Type: DRUG

Trastuzumab

Intervention Type: DRUG

Retifanlimab

Intervention Type: DRUG

Cisplatin

Intervention Type: DRUG

Other Intervention Names

INCB054828; INCMGA00012

Eligibility Criteria

Inclusion Criteria

1. Male or female subjects, age 18 years or older on day of signing consent

2. Part 1: Any advanced solid tumor malignancy; Part 2: Subjects with squamous non-small cell lung cancer, cholangiocarcinoma/gastric cancer, urothelial cancer, breast/endometrial cancer, multiple myeloma, or MPNs that have a tumor or malignancy that has been evaluated and confirmed to harbor genetic alterations in FGF or FGFR genes. A subject's fibroblast growth factor (FGF) or fibroblast growth factor receptor (FGFR) alteration may be based on local or central laboratory results. Part 3: Dose finding: subjects with solid tumor malignancies who qualify for combo therapy; dose-expansion: FGF/FGFR+ subjects qualified to receive combo therapy

3. Has progressed after prior therapy and there is no further effective standard anticancer therapy available (including subject refuses or is intolerant)

4. Life expectancy > 12 weeks

5. Eastern Cooperative Oncology Group (ECOG) performance status:

• Part 1: 0 or 1
• Part 2 and 3: 0, 1, or 2

Exclusion Criteria

1. Treatment with other investigational study drug for any indication for any reason, or receipt of anticancer medications within 21 days or 5 half-lives before first dose of study drug

2. Prior receipt of a selective FGFR inhibitor

3. History of a calcium/phosphate homeostasis disorder

4. History and/or current evidence of ectopic mineralization/calcification

5. Current evidence of corneal disorder/keratopathy

6. Has a history or presence of inadequate liver, renal, hematopoietic and/or cardiac function parameters outside protocol-defined range

7. Prior radiotherapy within 2 weeks of study treatment

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Incyte Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Luis Féliz, MD

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

University of Alabama At Birmingham Comprehensive Cancer Center

Birmingham, Alabama, United States

Cedars-Sinai Medical Center

West Hollywood, California, United States

Yale Cancer Center

New Haven, Connecticut, United States

Georgetown University Hospital

Washington D.C., District of Columbia, United States

Hematology Oncology Associates of the Tr

Port Saint Lucie, Florida, United States

Emory University - Winship Cancer Institute

Atlanta, Georgia, United States

University of Michigan Health System

Ann Arbor, Michigan, United States

Washington University School of Medicine

St Louis, Missouri, United States

John Theurer Cancer Center, Hackensack University Medical Center

Hackensack, New Jersey, United States

Northwell Health - Monter Cancer Center

New Hyde Park, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Ohio State University - Wexner Medical Center

Columbus, Ohio, United States

Signal Point Clinical Research Center

Middletown, Ohio, United States

Greenville Health System Cancer Institute

Greenville, South Carolina, United States

Mary Crowley Cancer Research Ctr

Dallas, Texas, United States

Md Anderson Cancer Center

Houston, Texas, United States

South Texas Accelerated Research Therapeutics

San Antonio, Texas, United States

Baylor Scott & White Health

Temple, Texas, United States

The Finsen Centre National Hospital

Copenhagen, , Denmark

Countries

United States; Denmark

References

Subbiah V, Iannotti NO, Gutierrez M, Smith DC, Feliz L, Lihou CF, Tian C, Silverman IM, Ji T, Saleh M. FIGHT-101, a first-in-human study of potent and selective FGFR 1-3 inhibitor pemigatinib in pan-cancer patients with FGF/FGFR alterations and advanced malignancies. Ann Oncol. 2022 May;33(5):522-533. doi: 10.1016/j.annonc.2022.02.001. Epub 2022 Feb 14.

Reference Type: DERIVED

PMID: 35176457 (View on PubMed)

Gong X, Ji T, Liu X, Chen X, Yeleswaram S. Evaluation of the clinical cardiac safety of pemigatinib, a fibroblast growth factor receptor inhibitor, in participants with advanced malignancies. Pharmacol Res Perspect. 2022 Feb;10(1):e00906. doi: 10.1002/prp2.906.

Reference Type: DERIVED

PMID: 34951522 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

INCB 54828-101

Identifier Type: -

Identifier Source: org_study_id