Open-Label, Dose-Escalation Study of Pemigatinib in Subjects With Advanced Malignancies - (FIGHT-101)
Purpose
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
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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
- 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
Study Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
Arm | Description | Assigned Intervention |
---|---|---|
Experimental 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. |
|
Experimental 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. |
|
Experimental 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. |
|
Experimental 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. |
|
Experimental 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. |
|
Experimental 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. |
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Experimental 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. |
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Experimental 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. |
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Experimental 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. |
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Experimental 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. |
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Experimental 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. |
|
Experimental 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. |
|
Experimental 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. |
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Experimental 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. |
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Experimental 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. |
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Experimental 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. |
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Experimental 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. |
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Experimental 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. |
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Experimental 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. |
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Experimental 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. |
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Experimental 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. |
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Experimental 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. |
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Experimental 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. |
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Experimental 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. |
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Experimental 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. |
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More Details
- Status
- Terminated
- Sponsor
- Incyte Corporation