Pemigatinib + Afatinib in Advanced Refractory Solid Tumors

ConditionsAdvanced Solid Tumor Unresectable Solid Tumor Metastatic Solid Tumor Cholangiocarcinoma

Trial statusRecruiting

Trial phasePhase 1

Trial typeInterventional

Biological sexAll

Age18+

SponsorMassachusetts General Hospital

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

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
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

Treatment groups

32 Participants

are divided into 3 treatment groups

Group A: DOSE ESCALATION PHASE 1A PEMIGATINIB + AFATINIBExperimental treatment 2 interventions

Group B: COHORT 1: EXPANSION PHASE 1B COHORT 1 MTD/RP2D PEMIGATINIB + AFATINIB FGFR INHIBITOR-NAIVEExperimental treatment 2 interventions

Group C: COHORT 2: EXPANSION PHASE 1B COHORT 2 MTD/RP2D PEMIGATINIB + AFATINIB FGFR INHIBITOR-PRETREATEDExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

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)

Time frame

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

Time frame