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703638005

New Medicines

Xalkori ALK-positive anaplastic large cell lymphoma - second line or greater

Information

Xalkori
Licence extension / variation
Pfizer
Pfizer

Development and Regulatory status

Phase II Clinical Trials
Recommended for approval (Positive opinion)
Launched
Sep 22EU CHMP recommends a change to the indications for Xalkori to include use for “the treatment of paediatric patients (age ≥6 to <18 years) with relapsed or refractory systemic anaplastic lymphoma kinase (ALK)‑positive anaplastic large cell lymphoma (ALCL)” and for “the treatment of paediatric patients (age ≥6 to <18 years) with recurrent or refractory anaplastic lymphoma kinase (ALK)‑positive unresectable inflammatory myofibroblastic tumour (IMT)” [10].
Oct 21Currently pre-registration in EU for a licence extension to include treatment of paediatric patients (age ≥ 6 to < 18 years) with relapsed or refractory systemic anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) and with unresectable, recurrent, or refractory ALK-positive inflammatory myofibroblastic tumour (IMT) for XALKORI based on the results from studies ADVL0912 and A8081013. The CHMP agreed to the request from the applicant for an extension to the clock stop to respond to the request for supplementary information adopted in September 2021 [9].
Jan 21US FDA approves crizotinib for treatment of ALK-positive anaplastic large cell lymphoma (ALCL) in children aged 1 year and above and young adults [8].
Sep 20Pfizer has agreed on a Pediatric Investigational Plan (PIP) for crizotinib for relapsed or refractory systemic ALK-positive anaplastic large cell lymphoma with European Medicines Agency [6].
Sep 20FDA accepts sNDA for Xalkori (crizotinib) for treatment ofpaediatric ALK-positive anaplastic large cell lymphoma [6].
Oct 19Not listed in Pfizer pipeline [5].
May 18Granted breakthrough therapy status in the US [1].

Category

An oral, first-in-class, inhibitor of receptor tyrosine kinases, including anaplastic lymphoma kinase (ALK), ROS1 (c-ros oncogene 1) and hepatocyte growth factor receptor (HGFR, c-Met) [2].
Anaplastic large cell lymphoma (ALCL) is a rare type of non-Hodgkin lymphoma (NHL), but one of the more common subtypes of T-cell lymphoma. ALCL comprises about 2% of all NHLs and approximately 20% of all T-cell lymphomas. Patients with systemic ALCL may be ALK-positive or ALK-negative. Both of these lymphomas are treated as aggressive, yet many patients still relapse or require alternative treatment approaches. ALK-positive ALCL usually affects children and young adults [3].
ALK-positive anaplastic large cell lymphoma - second line or greater
Oral

Trial or other data

May 20Results posted for PI/II study (NCT00939770). Overall response in the ALCL cohort (n=10) is 70% [7].
Dec 19No results posted yet for PI/II study (NCT00939770) [4].
Dec 18PI/II study (NCT00939770) completes [4].
Nov 18PI study (NCT01121588) is due to complete collection of primary outcome data in Dec 19 [4].
May 18Breakthrough therapy status in the US was granted based on data from PIb and PII trials, Study ADVL0912 (NCT00939770) and Study A8081013 (NCT01121588) [3].

Evidence based evaluations

Xalkori Unresectable, recurrent or refractory inflammatory ALK-positive myofibroblastic tumours

Information

Xalkori
Licence extension / variation
Pfizer
Pfizer

Development and Regulatory status

None
None
Launched
Yes
Jul 22Has orphan drug status for IMT. US approval is for adult and pediatric patients 1 year of age and older [3].
Jul 22FDA approves crizotinib to treat unresectable, recurrent or refractory inflammatory ALK-positive myofibroblastic tumours that cannot be removed by surgery and are progressing despite prior treatment [2].

Category

An oral, first-in-class, inhibitor of receptor tyrosine kinases, including anaplastic lymphoma kinase (ALK), ROS1 (c-ros oncogene 1) and hepatocyte growth factor receptor (HGFR, c-Met)
Inflammatory myofibroblastic tumour (IMT) represents an extremely rare type of inflammatory pseudo-tumour that appears most commonly in children and young individuals with a prevalence ranging from 0.04% to 0.7% irrespective of the gender and race of the world population [1].
Unresectable, recurrent or refractory inflammatory ALK-positive myofibroblastic tumours
Oral

Trial or other data

Jul 22 The safety and efficacy of crizotinib were evaluated in two multicentre, single-arm, open-label trials that included 14 paediatric patients from trial ADVL0912 (NCT00939770) and 7 adult patients from trial A8081013 (NCT01121588) with unresectable, recurrent, or refractory ALK-positive IMT. The major efficacy outcome measure of these trials was objective response rate (ORR). For the 14 paediatric patients, a total of 12 of the 14 patients (86%, 95% CI: 57, 98) experienced an objective response, assessed by an independent review committee. For the 7 adult patients, 5 patients had objective responses. The most common adverse reactions (≥35%) in paediatric patients were vomiting, nausea, diarrhoea, abdominal pain, rash, vision disorder, upper respiratory tract infection, cough, pyrexia, musculoskeletal pain, fatigue, oedema, constipation, and headache. The most frequent adverse reactions (≥35%) in adult patients were vision disorders, nausea, and oedema. The recommended crizotinib dose in adult patients is 250 mg orally twice daily until disease progression or unacceptable toxicity. The recommended paediatric dose is 280 mg/m2 orally twice daily until disease progression or unacceptable toxicity [3].