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Advanced Solid TumorPhase 1NCT06302621

Pemigatinib + Afatinib in Advanced Refractory Solid Tumors

A Phase 1 study testing Afatinib and Pemigatinib in people with Advanced Solid Tumor and Unresectable Solid Tumor, run by Massachusetts General Hospital at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Afatinib and Pemigatinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
1 siteUnited States
Study dates
17 Apr 2024to 1 Dec 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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
  • Hemoglobin ≥ 9 g/dL (≥ 90 g/L)
  • Absolute Neutrophil Count ≥ 1.5 x 109/L
  • Platelets ≥ 75 x 109/L
  • INR or PT, aPTT or PTT ≤ 1.5 × ULN unless participant is receiving anticoagulant therapy
  • NOTE: Transfusions to increase a patient's hemoglobin level or initiation of erythropoietin or G-CSF therapy to meet enrollment criteria are not allowed in the 14 days preceding the first dose of study drug. If a patient receives transfusions, erythropoietin, or G-CSF therapy ≥ 14 days prior to the first dose, the hematologic criteria listed above must be met following the 14-day window and prior to the first dose of study therapy
  • Dose expansion cohort 1: Patients should fulfill the eligibility criteria above for all patients in addition to the following:
  • Histologically or cytologically confirmed diagnosis of advanced or metastatic cholangiocarcinoma
  • No prior treatment with a selective FGFR inhibitor treatment
  • FGFR2 fusion, in-frame rearrangement, or extracellular domain in-frame deletion on tumor profiling in tumor tissue as determined by testing routinely performed on tumor biopsy at a CLIA or other similarly certified laboratory. If the FGFR alteration is present on ctDNA analysis alone, the patient may be eligible with principal investigator approval.
  • An archived tumor tissue sample is available in patients not undergoing fresh tumor biopsy. Patients who do not have adequate archival tumor tissue available are required to undergo a fresh tumor biopsy. If a fresh biopsy cannot be safely performed, the patient may be eligible with principal investigator approval.
  • Dose expansion cohort 2: Patients should fulfill the eligibility criteria above for all patients in addition to the following:
  • Histologically or cytologically confirmed diagnosis of advanced or metastatic cholangiocarcinoma
  • Prior FGFR inhibitor treatment at any time prior to treatment start is required
  • FGFR2 fusion, in-frame rearrangement, or extracellular domain in-frame deletion for which they derived clinical benefit (objective response of any duration or stable disease for at least 6 months) from prior FGFR inhibitor therapy, as determined by testing routinely performed on tumor biopsy at a CLIA or other similarly certified laboratory. If the FGFR alteration is present on ctDNA analysis alone, the patient may be eligible with principal investigator approval
  • An archived tumor tissue sample after progression on or intolerance of prior FGFR inhibitor available in patients not undergoing fresh tumor biopsy. Patients who do not have adequate archival tumor tissue available are required to undergo a fresh tumor biopsy. If a fresh biopsy cannot be safely performed, the patient may be eligible with principal investigator approval.

Who cannot join

  • 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.
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  • 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
  • Patients with ascites requiring serial paracenteses
  • Active central nervous system (CNS) metastases are not eligible. Patients with asymptomatic and treated brain metastases may participate provided that they are stable for ≥ 2 months. Patients with suspected or confirmed leptomeningeal disease are not eligible even if treated. Patients with glioblastoma multiforme (GBM) are not eligible.
  • Clinically significant, active cardiovascular disease such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) classification of 3, unstable angina or poorly controlled arrhythmia, or history of myocardial infarction within 6 months prior to planned start of pemigatinib and afatinib
  • Fridericia's corrected QT interval (QTcF) > 480 ms on ECG conducted during Screening, or history of torsades de pointes or personal or family history of prolonged QT syndrome.Correction of suspected drug-induced QTcF prolongation can be attempted at the investigator's discretion and only if clinically safe to do so with either discontinuation of the offending drug or switch to another drug not known to be associated with QTcF prolongation.
  • Active uncontrolled systemic bacterial, viral, fungal or parasitic infection (except for fungal nail infection), or other clinically significant active disease process which in the opinion of the investigator and the sponsor-investigator makes it undesirable for the patient to participate in the trial. Screening for chronic conditions is not required.
  • Active hepatitis B virus (HBV)
  • -- Note: Controlled (treated) hepatitis will be allowed if they meet the following criteria: antiviral therapy for HBV must be given for at least 1 month prior to first dose of study drug, and HBV viral load must be less than 2000 IU/ml (104 copies/ml) prior to the first dose of study drug. Those on active HBV therapy with viral loads under 2000 IU/ml (104 copies/ml) should stay on antiviral therapy throughout the study treatment.
  • Known human immunodeficiency virus (HIV) and on anti-retroviral therapy for HIV(excluded due to potential drug-drug interactions between anti-retroviral medications and study treatment but HIV itself is not an exclusion).
  • Known or suspected active drug or alcohol use
  • Concomitant treatment with known strong p-gp inhibitor.
  • Use of any potent CYP3A4 inhibitors or inducers or moderate CYP3A4 inducers within 14 days or 5 half-lives (whichever is longer) before the first dose of study treatment.
  • -- Note: Moderate CYP3A4 inhibitors are not prohibited
  • Pregnancy during the study or within 30 days of the last dose of study intervention. Also excluded are any persons of childbearing potential, including men who are able to father a child, who are unwilling to use a medically acceptable method of contraception during the trial (see below section 3.3). Lactation and breastfeeding during the study or within 30 days of the last dose of study intervention is also not allowed. Female patients must have a negative pregnancy test (B-HCG test in urine or serum) prior to commencing study treatment.
  • Unable to swallow pills
  • Any other concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the study drug. Patients unable or deemed by the investigator as unlikely to comply with the protocol are also excluded.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Haley Ellis, MD contact

617-724-4000

hellis@mgh.harvard.edu

United States1 site, 1 recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts, 02115

    Haley Ellis, MD, 617-724-4000, hellis@mgh.harvard.edu

    Haley Ellis, MD

    Recruiting

Other trials in United States

About this study

Official title: A Phase Ia/Ib Study of the Combination of the FGFR Inhibitor Pemigatinib and the EGFR Inhibitor Afatinib in Advanced Refractory Solid Tumors

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.

Read the detailed description

This is an open-label phase Ia/Ib study to evaluate safety, tolerability and preliminary efficacy of the combination of pemigatinib and afatinib in patients with FGFR-altered refractory advanced solid tumors.

This study includes 2 parts: phase 1a dose escalation and phase 1b dose expansion.

  • In the phase 1a dose escalation study patients with FGFR-altered refractory advanced refractory solid tumors will be enrolled.
  • 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.

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.

This research study involves the study drugs Afatinib and Pemigatinib.

Participants will receive study treatment for as long there is benefit and no unacceptable side effects. Participants will be followed for up to 1 year. It is expected that up to 32 people will take part in this research study.

This research study is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drug is being studied.

The U.S. Food and Drug Administration (FDA) has not approved afatinib for this specific disease but it has been approved for other uses. The U.S. Food and Drug Administration (FDA) has approved pemigatinib for cholangiocarcinoma with an FGFR2 rearrangement or fusion.

The FDA has not approved the combination of afatinib and pemigatinib as a treatment for any disease.

Being tested
Afatinib, Pemigatinib
Keywords
Advanced Solid Tumor, Unresectable Solid Tumor, Metastatic Solid Tumor, Cholangiocarcinoma
Medical subject headings
Neoplasm Metastasis, Cholangiocarcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AfatinibDrug

    Also called Gilotrif™

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

  • PemigatinibDrug

    Also called Pemazyre

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

Study groups in NCT06302621
Study groupRoleWhat they receive
DOSE ESCALATION PHASE 1A PEMIGATINIB + AFATINIBExperimentalIn 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.
Receives: Drug: Afatinib; Drug: Pemigatinib
COHORT 1: EXPANSION PHASE 1B COHORT 1 MTD/RP2D PEMIGATINIB + AFATINIB FGFR INHIBITOR-NAIVEExperimentalIn 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.
Receives: Drug: Afatinib; Drug: Pemigatinib
COHORT 2: EXPANSION PHASE 1B COHORT 2 MTD/RP2D PEMIGATINIB + AFATINIB FGFR INHIBITOR-PRETREATEDExperimentalIn 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.
Receives: Drug: Afatinib; Drug: Pemigatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Measured: Through Cycle 1 (21 Days)

  2. 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

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

Secondary outcomes (9)

  1. Disease Control Rate

    Defined as the proportion of patients achieving CR, PR or stable disease (SD) as assessed per RECIST v1.1

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

  2. Duration of Response

    Defined as the time from first documentation of CR or PR by RECIST v1.1 until the time of first documentation of progressive disease (PD) evaluated using RECIST v1.1 or death due to any cause

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

  3. Overall Survival

    Defined as the time from date of first dose of study treatment to the date of death by any cause.

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

  4. Progression-free Survival

    Defined as the time from date of first dose to the earlier date of assessment of progression or death by any cause in the absence of progression, based on the time of first documentation of PD per RECIST v1.1

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

  5. Best Overall Response

    The best response recorded per RECIST 1.1, from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started).

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

  6. Time to response

    The time from the date of the first dose to the first objective tumor response (tumor shrinkage of ≥30%) observed for patients who achieved a CR or PR.

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

  7. Treatment Related Adverse Events

    Number of Participants with treatment-related adverse events as assessed by CTCAE v5.0 (National Cancer Institute's Common Terminology Criteria for Adverse Events, version 5.0)

    Measured: Each visit until 30 days after study discontinuation.

  8. Maximum Plasma Concentration [Cmax]) and C trough of pemigatinib and afatinib

    To characterize the Pharmacokinetics (PK) properties of the combination of pemigatinib and afatinib

    Measured: Cycle 1 day 1 and Cycle 1 day 8

  9. Molecular correlates of response

    Circulating tumor DNA

    Measured: Through study completion, an average of 6 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Mar 2024
  2. Study start17 Apr 2024
  3. Primary completion1 Dec 2027 (estimated)
  4. Study completion1 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
32 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06302621
Sponsor's protocol ID
21-725
Status last verified
Sep 2026
First submitted
10 Aug 2022
Last updated
23 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Publications

  • 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.

    PubMed 35420673

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Afatinib and Pemigatinib in people with Advanced Solid Tumor and Unresectable Solid Tumor, run by Massachusetts General Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 23 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Haley Ellis, MD (617-724-4000, hellis@mgh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (MTD) (time frame: Through Cycle 1 (21 Days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06302621, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2026.

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