Pemigatinib + Afatinib in Advanced Refractory Solid Tumors

NCT06302621 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 21-725
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

This study is researching whether the combination of Afatinib and Pemigatinib is safe and effective in FGFR altered unresectable or metastatic advanced solid tumors. The study is also trying to discover the highest doses of the study drugs that can be administered without causing any intolerable side effects. This research study involves the study drugs Afatinib and Pemigatinib.

Conditions

Advanced Solid Tumor; Unresectable Solid Tumor; Metastatic Solid Tumor; Cholangiocarcinoma

Keywords

Advanced Solid Tumor; Unresectable Solid Tumor; Metastatic Solid Tumor; Cholangiocarcinoma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD)

  All patients in the dose-escalation part who have received ≥ 75% (21 days) of study drug and completed Cycle 1 through Cycle 1 Day 21 or experienced a dose limiting toxicity (DLT)

  Through Cycle 1 (21 Days)

• Objective response rate (ORR)

  Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) in patients with FGFR2-fusion, rearrangement or in-frame deletion positive intrahepatic cholangiocarcinoma. Defined as the proportion of patients achieving Complete response (CR) and partial response(PR) per RECIST v1.1

  Baseline, Every 9 weeks during treatment and Off Study up to 1 year

Secondary Outcomes (9)

• Disease Control Rate

  Baseline, Every 9 weeks during treatment and Off Study up to 1 year

• Duration of Response

  Baseline, Every 9 weeks during treatment and Off Study up to 1 year

• Overall Survival

  Baseline, Every 9 weeks during treatment and Off Study up to 1 year

• Progression-free Survival

  Baseline, Every 9 weeks during treatment and Off Study up to 1 year

• Best Overall Response

  Baseline, Every 9 weeks during treatment and Off Study up to 1 year

Study Arms (3)

DOSE ESCALATION PHASE 1A PEMIGATINIB + AFATINIB

EXPERIMENTAL

In the phase 1a dose escalation study participants with FGFR-altered refractory advanced solid tumors will be enrolled. This research study involves the study drugs Afatinib and Pemigatinib.

Drug: Afatinib; Drug: Pemigatinib

COHORT 1: EXPANSION PHASE 1B COHORT 1 MTD/RP2D PEMIGATINIB + AFATINIB FGFR INHIBITOR-NAIVE

EXPERIMENTAL

In the phase Ib dose expansion study, patients with FGFR-altered cholangiocarcinoma will be recruited into 2 cohorts: FGFR inhibitor-naïve cholangiocarcinoma and FGFR-inhibitor-pretreated and resistant cholangiocarcinoma. Cohort 1 will enroll patients with FGFR inhibitor-naïve cholangiocarcinoma. This research study involves the study drugs Afatinib and Pemigatinib.

Drug: Afatinib; Drug: Pemigatinib

COHORT 2: EXPANSION PHASE 1B COHORT 2 MTD/RP2D PEMIGATINIB + AFATINIB FGFR INHIBITOR-PRETREATED

EXPERIMENTAL

In the phase Ib dose expansion study, patients with FGFR-altered cholangiocarcinoma will be recruited into 2 cohorts: FGFR inhibitor-naïve cholangiocarcinoma and FGFR-inhibitor-pretreated and resistant cholangiocarcinoma. Cohort 2 will enroll patients with FGFR-inhibitor-pretreated and resistant cholangiocarcinoma. This research study involves the study drugs Afatinib and Pemigatinib.

Drug: Afatinib; Drug: Pemigatinib

Interventions

Afatinib DRUG

Each study treatment cycle lasts 21 days: Afatinib, oral, once daily, per protocol determined number of days per cycle and per protocol determined dosage

Also known as: Gilotrif™

COHORT 1: EXPANSION PHASE 1B COHORT 1 MTD/RP2D PEMIGATINIB + AFATINIB FGFR INHIBITOR-NAIVE; COHORT 2: EXPANSION PHASE 1B COHORT 2 MTD/RP2D PEMIGATINIB + AFATINIB FGFR INHIBITOR-PRETREATED; DOSE ESCALATION PHASE 1A PEMIGATINIB + AFATINIB

Pemigatinib DRUG

Each study treatment cycle lasts 21 days: Pemigatinib, oral, once daily, per protocol determined number of days per cycle and per protocol determined dosage

Also known as: Pemazyre

COHORT 1: EXPANSION PHASE 1B COHORT 1 MTD/RP2D PEMIGATINIB + AFATINIB FGFR INHIBITOR-NAIVE; COHORT 2: EXPANSION PHASE 1B COHORT 2 MTD/RP2D PEMIGATINIB + AFATINIB FGFR INHIBITOR-PRETREATED; DOSE ESCALATION PHASE 1A PEMIGATINIB + AFATINIB

Eligibility Criteria

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

You may qualify if:

• All Patients
• Unresectable or metastatic, histologically confirmed advanced solid tumor, where standard curative or palliative measures are no longer effective or are not considered appropriate or safe in the opinion of the investigator.
• FGFR1-3 fusion, rearrangement, activating mutation, or FGFR2 extracellular domain in-frame deletions on tumor profiling in tumor tissue as determined by testing routinely performed at a Clinical Laboratory Improvement Amendments (CLIA) or other similarly certified laboratory. If the FGFR alteration is present on circulating tumor DNA (ctDNA) analysis alone, the patient may be eligible with principal investigator approval. Additional mutations may be considered with principal investigator approval.
• Eastern Cooperative Oncology Group (ECOG) 0-1.
• At least 18 years of age.
• Ability to swallow tablets.
• Life expectancy \>/=3 months
• Ability to comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation.
• Patients with cholangiocarcinoma must have adequate biliary drainage (per investigator's discretion), with no evidence of ongoing infection.
• Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and for 3 months following the last dose of study treatment.
• Measurable or non-measurable disease as determined by RECIST 1.1.
• Adequate organ function defined as:
• ALT or AST ≤ 3 × the ULN in the absence of liver metastases, OR ≤ 5 × ULN with documented liver metastases
• Total bilirubin ≤ 2.0 × ULN in the absence of Gilbert's Disease, OR ≤ 3 × ULN with Gilbert's Disease provided direct bilirubin is ≤ ULN
• Serum Creatinine ≤ 1.5 × ULN OR calculated creatinine clearance ≥ 60ml/min

You may not qualify if:

• Known hypersensitivity to afatinib or pemigatinib or excipients of pemigatinib
• For patients treated with a prior FGFR inhibitor, those with known activating mutation(s) in the FGFR2 kinase domain on ctDNA or biopsy analysis within 8 weeks of start of study drugs; activating mutations in the FGFR2 kinase domain seen on ctDNA or biopsy analysis prior to the 8-week timepoint may be allowed after discussion with the study PI.
• Systemic or liver-directed anticancer therapy within 2 weeks; or anticancer monoclonal antibody within 4 weeks prior to planned start of pemigatinib and afatinib.
• Patient has adverse events from prior therapy that have not resolved to ≤ grade 1; exceptions for non-clinically meaningful adverse events (AEs) can be made with input from the principal investigator.
• Major surgery within 4 weeks prior to planned start of pemigatinib and afatinib (tumor biopsy, biliary stent or catheter placement, and feeding tube placement are not considered major surgical procedures).
• Received prior palliative non-CNS radiation within 2 weeks or extended-field radiation administered within 4 weeks of first dose of study drug. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. Fibrotic pulmonary disease from prior radiotherapy is permissible with approval of the study PI.
• Known pre-existing interstitial lung disease
• Current hypovitaminosis D requiring supraphysiologic (eg 50,000 IU/weekly) to replenish the deficiency. Vitamin D supplements are allowed.
• History and/or current evidence of clinically significant ectopic mineralization/calcification or non-tumor related alteration of calcium-phosphorus homeostasis.
• History and/or current evidence of clinically significant corneal or retinal disorder confirmed by ophthalmological examination
• Child-Pugh B and C cirrhosis
• Chronic nausea, vomiting, or diarrhea considered to be clinically significant in the opinion of the investigator. This includes significant or recent gastrointestinal disorders with diarrhea as a major symptom
• Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug.
• Patients with a history of another primary malignancy that is currently clinically significant, and has potential for metastases or currently requires active intervention (except for gonadotropin-releasing hormone (GnRH) or luteinizing hormone-releasing hormone (LH-RH) agonists in prostate cancer or hormonal therapy in breast cancer
• Have history of hepatic encephalopathy of any grade

Sponsors & Collaborators

• Incyte Corporation: collaborator
• Massachusetts General Hospital: lead
• Boehringer Ingelheim: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Related Publications (1)

• Wu Q, Zhen Y, Shi L, Vu P, Greninger P, Adil R, Merritt J, Egan R, Wu MJ, Yin X, Ferrone CR, Deshpande V, Baiev I, Pinto CJ, McLoughlin DE, Walmsley CS, Stone JR, Gordan JD, Zhu AX, Juric D, Goyal L, Benes CH, Bardeesy N. EGFR Inhibition Potentiates FGFR Inhibitor Therapy and Overcomes Resistance in FGFR2 Fusion-Positive Cholangiocarcinoma. Cancer Discov. 2022 May 2;12(5):1378-1395. doi: 10.1158/2159-8290.CD-21-1168.

  PMID: 35420673 BACKGROUND

MeSH Terms

Conditions

Neoplasm Metastasis; Cholangiocarcinoma

Interventions

Afatinib; pemigatinib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Haley Ellis, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Haley Ellis, MD

CONTACT

617-724-4000; hellis@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 10, 2022
• First Posted: March 12, 2024
• Study Start: April 17, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: January 15, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (1)