Trial Outcomes & Findings for Real World Data Collection Pediatric Neuroblastoma Treated With Lorlatinib (NCT NCT04753658)

Last Updated: 2024-09-23

Results Overview

Tumor response was collected by the data collection tool (DCT) and responses included complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). As per International Neuroblastoma Response Criteria (INRC): CR=\<10 millimeter (mm) residual soft tissue at primary site and complete resolution of metaiodobenzylguanidine (MIBG) or \[18F\] fluorodeoxyglucose (FDG)/positron emission tomography (PET) uptake (for MIBG-nonavid tumors) at primary site; PR: \>=30% decrease in longest diameter (LD) of primary site \& MIBG or FDG-PET uptake at primary site stable, improved, or resolved; SD: neither sufficient shrinkage for PR nor sufficient increase for PD at the primary site. PD greater than 20% increase in longest diameter taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study) and minimum absolute increase of 5 mm in longest dimension. One participant may have more than one tumor response.

Recruitment status

TERMINATED

Target enrollment

15 participants

Primary outcome timeframe

From start of lorlatinib treatment until CR, PR, SD or PD, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)

Results posted on

2024-09-23

Participant Flow

Participants with anaplastic lymphoma kinase (ALK)-aberrant neuroblastoma who initiated treatment with lorlatinib as part of expanded access program were included in this non-interventional study. Data was collected using the data collection tool (DCT).

Participant milestones

Participant milestones
Measure	Lorlatinib Participants with ALK-aberrant neuroblastoma who initiated treatment with lorlatinib as part of an expanded access program were included. Data was collected on a continual basis until discontinuation of treatment with lorlatinib, death, loss to follow-up or end of study, whichever occurred first.
Overall Study STARTED	15
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Lorlatinib Participants with ALK-aberrant neuroblastoma who initiated treatment with lorlatinib as part of an expanded access program were included. Data was collected on a continual basis until discontinuation of treatment with lorlatinib, death, loss to follow-up or end of study, whichever occurred first.
Overall Study Progressive disease	7
Overall Study Other	7
Overall Study Adverse Event	1

Baseline Characteristics

Real World Data Collection Pediatric Neuroblastoma Treated With Lorlatinib

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lorlatinib n=15 Participants Participants with ALK-aberrant neuroblastoma who initiated treatment with lorlatinib as part of an expanded access program were included. Data was collected on a continual basis until discontinuation of treatment with lorlatinib, death, loss to follow-up or end of study, whichever occurred first.
Age, Continuous	13.23 Years STANDARD_DEVIATION 11.553 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: From start of lorlatinib treatment until CR, PR, SD or PD, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)

Population: All participants for whom data was collected using the data collection tool and observed in this study were included in the analysis.

Outcome measures

Outcome measures
Measure	Lorlatinib n=15 Participants Participants with ALK-aberrant neuroblastoma who initiated treatment with lorlatinib as part of an expanded access program were included. Data was collected on a continual basis until discontinuation of treatment with lorlatinib, death, loss to follow-up or end of study, whichever occurred first.
Number of Participants According to Tumor Response of Primary Tumor (Soft Tissue) CR	3 Participants
Number of Participants According to Tumor Response of Primary Tumor (Soft Tissue) Missing	7 Participants
Number of Participants According to Tumor Response of Primary Tumor (Soft Tissue) PR	3 Participants
Number of Participants According to Tumor Response of Primary Tumor (Soft Tissue) SD	5 Participants
Number of Participants According to Tumor Response of Primary Tumor (Soft Tissue) PD	2 Participants

PRIMARY outcome

Population: All participants for whom data was collected using the data collection tool and observed in this study were included in the analysis.

Tumor response collected by DCT.Response included CR=resolution of all sites of disease; PR:\>=30% decrease in sum of diameter of non-primary (NP) target lesion (TL) compared to baseline, non-target (NT) lesion may be stable/small in size, no new lesion,\>=50% reduced MIBG absolute(abs) bone score (BS) (relative MIBG BS\>=0.1 to \<=0.5)/\>=50% reduced number of FDG-PET avid bone lesion; PD:new soft tissue lesion (STL) detected by computed tomography (CT)/magnetic resonance imaging (MRI) that's MIBG avid/FDG-PET avid, new STL on anatomic imaging, biopsied, confirmed as neuroblastoma(NB)/ganglioneuroblastoma(GNB),new bone site:MIBG avid/FDG-PET avid (for MIBG non-avid tumor) with CT/MRI finding consistent with tumor/confirmed histologically as NB/GNB; \>20% increase in LD as reference smallest sum on study,minimum abs. increase of 5mm in sum of diameter of target STL; SD:No sufficient (suff) shrinkage for PR/suff increase for PD of NP lesion.One participant may have more than 1 tumor response

Outcome measures

Outcome measures
Measure	Lorlatinib n=15 Participants Participants with ALK-aberrant neuroblastoma who initiated treatment with lorlatinib as part of an expanded access program were included. Data was collected on a continual basis until discontinuation of treatment with lorlatinib, death, loss to follow-up or end of study, whichever occurred first.
Number of Participants According to Tumor Response of Soft Tissue Metastasis and Bone Metastasis CR	5 Participants
Number of Participants According to Tumor Response of Soft Tissue Metastasis and Bone Metastasis PR	5 Participants
Number of Participants According to Tumor Response of Soft Tissue Metastasis and Bone Metastasis SD	5 Participants
Number of Participants According to Tumor Response of Soft Tissue Metastasis and Bone Metastasis PD	7 Participants
Number of Participants According to Tumor Response of Soft Tissue Metastasis and Bone Metastasis Missing	2 Participants

PRIMARY outcome

Timeframe: From start of lorlatinib treatment until CR, PR, MD or SD, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)

Population: All participants for whom data was collected using the data collection tool and observed in this study were included in the analysis.

Bone marrow response was collected by the DCT and responses included CR, PR, minimal disease (MD) and SD. As per INRC, CR= bone marrow with no tumor infiltration upon reassessment, independent of baseline tumor involvement; PD= bone marrow without tumor infiltration that became \> 5% tumor infiltration upon reassessment; or bone marrow with tumor infiltration that increased by \> 2 fold and had \> 20% tumor infiltration upon reassessment; MD= Bone marrow with less than or equal to (\<=) 5% tumor infiltration and remained \> 0 to \<= 5% tumor infiltration upon reassessment; or bone marrow with no tumor infiltration that became \<= 5% tumor infiltration upon reassessment; or bone marrow with \>20% tumor infiltration that had \> 0 to \<= 5% tumor infiltration upon reassessment and SD= bone marrow with tumor infiltration that remained positive with \> 5% tumor infiltration upon reassessment but did not meet CR, MD or PD criteria.

Outcome measures

Outcome measures
Measure	Lorlatinib n=15 Participants Participants with ALK-aberrant neuroblastoma who initiated treatment with lorlatinib as part of an expanded access program were included. Data was collected on a continual basis until discontinuation of treatment with lorlatinib, death, loss to follow-up or end of study, whichever occurred first.
Number of Participants According to Bone Marrow Response PR	0 Participants
Number of Participants According to Bone Marrow Response CR	2 Participants
Number of Participants According to Bone Marrow Response MD	1 Participants
Number of Participants According to Bone Marrow Response SD	0 Participants
Number of Participants According to Bone Marrow Response Missing	12 Participants

PRIMARY outcome

Timeframe: From start of lorlatinib treatment until CR, PR, MR, SD or PD, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)

Population: All participants for whom data was collected using the data collection tool and observed in this study were included in the analysis.

Objective response was collected by the DCT and comprised of responses in 3 components based on INRC: primary tumor, soft tissue and bone metastases and bone marrow, CR=All components met criteria for CR; PR=PR in at least one component and all other components are either CR, MD (bone marrow), PR (soft tissue or bone), or not involved (NI); no component with PD; Minor response (MR) = PR or CR in at least one component but at least one other component; no component with PD; SD= SD in one component with no better than SD or NI in any other component; PD=Any component with PD. One participant may have more than one tumor response.

Outcome measures

Outcome measures
Measure	Lorlatinib n=15 Participants Participants with ALK-aberrant neuroblastoma who initiated treatment with lorlatinib as part of an expanded access program were included. Data was collected on a continual basis until discontinuation of treatment with lorlatinib, death, loss to follow-up or end of study, whichever occurred first.
Number of Participants According to Health Care Professional (HCP) Reported Objective Response CR	5 Participants
Number of Participants According to Health Care Professional (HCP) Reported Objective Response MR	1 Participants
Number of Participants According to Health Care Professional (HCP) Reported Objective Response SD	5 Participants
Number of Participants According to Health Care Professional (HCP) Reported Objective Response PD	9 Participants
Number of Participants According to Health Care Professional (HCP) Reported Objective Response PR	7 Participants

PRIMARY outcome

Population: All participants for whom data was collected using the data collection tool and observed in this study were included in the analysis.

Derived objective response was derived using rules based on responses in 3 components: primary tumor, soft tissue and bone metastases, and bone marrow. CR=All components met criteria for CR. PR=PR in at least one component and all other components are either CR, MD (in bone marrow), PR (soft tissue or bone) or not involved (NI; no component with PD). MR = PR or CR in at least one component but at least one other component with stable disease; no component with PD. SD = Stable disease in one component with no better than SD or NI in any other component; no component with PD. PD = Any component with PD.

Outcome measures

Outcome measures
Measure	Lorlatinib n=15 Participants Participants with ALK-aberrant neuroblastoma who initiated treatment with lorlatinib as part of an expanded access program were included. Data was collected on a continual basis until discontinuation of treatment with lorlatinib, death, loss to follow-up or end of study, whichever occurred first.
Number of Participants According to Derived Objective Response Not Evaluable	4 Participants
Number of Participants According to Derived Objective Response CR	2 Participants
Number of Participants According to Derived Objective Response PR	0 Participants
Number of Participants According to Derived Objective Response MR	0 Participants
Number of Participants According to Derived Objective Response PD	8 Participants
Number of Participants According to Derived Objective Response Missing	1 Participants

PRIMARY outcome

Timeframe: From start of lorlatinib treatment until CR, PR, MR, SD or PD, Up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)

Population: All participants for whom data was collected using the data collection tool and observed in this study were included in the analysis.

Best overall response based on HCP reported objective response comprised of responses (CR, PR, MR, SD and PD) in 3 components: primary tumor, soft tissue and bone metastases, and bone marrow. CR=All components met criteria for CR. PR=At least one component and all other components are either CR, MD (in bone marrow), PR (soft tissue or bone) or not involved (NI; no component with PD). MR = PR or CR in at least one component but at least one other component with stable disease; no component with PD. SD = It is in one component with no better than SD or NI in any other component PD = Any component with PD. Best overall response taking the HCP reported response observed up to the data cut-off date for a specific milestone.

Outcome measures

Outcome measures
Measure	Lorlatinib n=15 Participants Participants with ALK-aberrant neuroblastoma who initiated treatment with lorlatinib as part of an expanded access program were included. Data was collected on a continual basis until discontinuation of treatment with lorlatinib, death, loss to follow-up or end of study, whichever occurred first.
Number of Participants With Best Overall Response Based on HCP Reported Objective Response CR	5 Participants
Number of Participants With Best Overall Response Based on HCP Reported Objective Response PR	3 Participants
Number of Participants With Best Overall Response Based on HCP Reported Objective Response MR	1 Participants
Number of Participants With Best Overall Response Based on HCP Reported Objective Response SD	3 Participants
Number of Participants With Best Overall Response Based on HCP Reported Objective Response PD	3 Participants

PRIMARY outcome

Population: All participants for whom data was collected using the data collection tool and observed were included in the analysis.

Best overall response based on derived objective response comprised of responses (CR, PR, MR, SD and PD) in 3 components: primary tumor, soft tissue and bone metastases, and bone marrow. CR=All components met criteria for CR. PR=PR in at least one component and all other components are either CR, MD (in bone marrow), PR (soft tissue or bone) or not involved (NI; no component with PD). MR= PR or CR in at least one component but at least one other component with stable disease; no component with PD. SD= Stable disease in one component with no better than SD or NI in any other component; no component with PD. PD= Any component with PD.

Outcome measures

Outcome measures
Measure	Lorlatinib n=15 Participants Participants with ALK-aberrant neuroblastoma who initiated treatment with lorlatinib as part of an expanded access program were included. Data was collected on a continual basis until discontinuation of treatment with lorlatinib, death, loss to follow-up or end of study, whichever occurred first.
Number of Participants With Best Overall Response Based on Derived Objective Response PD	8 Participants
Number of Participants With Best Overall Response Based on Derived Objective Response CR	2 Participants
Number of Participants With Best Overall Response Based on Derived Objective Response Missing	5 Participants

PRIMARY outcome

Timeframe: From start of lorlatinib treatment until CR or PR, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)

Population: All participants for whom data was collected using the data collection tool and observed in this study were included in the analysis.

Overall response rate was defined as the percentage of participants with a best overall response of CR or PR. CR=All components (primary tumor, soft tissue and bone metastases, and bone marrow) met criteria for CR. PR=PR in at least one component and all other components are either CR, MD (in bone marrow), PR (soft tissue or bone) or not involved (NI; no component with PD). Two sided 95% confidence interval was based on Clopper Pearson method.

Outcome measures

Outcome measures
Measure	Lorlatinib n=15 Participants Participants with ALK-aberrant neuroblastoma who initiated treatment with lorlatinib as part of an expanded access program were included. Data was collected on a continual basis until discontinuation of treatment with lorlatinib, death, loss to follow-up or end of study, whichever occurred first.
Overall Response Rate Based on HCP Reported Response	53.3 Percentage of participants Interval 26.6 to 78.7

PRIMARY outcome

Timeframe: From start of lorlatinib treatment until CR or PR, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)

Population: All participants for whom data was collected using the data collection tool and observed in this study were included in the analysis. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Lorlatinib n=10 Participants Participants with ALK-aberrant neuroblastoma who initiated treatment with lorlatinib as part of an expanded access program were included. Data was collected on a continual basis until discontinuation of treatment with lorlatinib, death, loss to follow-up or end of study, whichever occurred first.
Overall Response Rate Based on Derived Response	13.3 Percentage of Participants Interval 1.7 to 40.5

PRIMARY outcome

Timeframe: From date of CR or PR until earliest date of PD or death or censoring date, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)

Population: All participants for whom data was collected using the data collection tool and observed in this study were included in the analysis.

Duration of HCP reported overall response was derived as (earliest date of disease progression or death minus earliest date of complete or partial response + 1)/30.4. Participants who had not progressed or died were censored at their last assessment date prior to the data cut-off date. CR=All components (primary tumor, soft tissue and bone metastases, and bone marrow) met criteria for CR. PR=PR in at least one component and all other components are either CR, MD (in bone marrow), PR (soft tissue or bone) or not involved. PD=Any component with PD.

Outcome measures

Outcome measures
Measure	Lorlatinib n=15 Participants Participants with ALK-aberrant neuroblastoma who initiated treatment with lorlatinib as part of an expanded access program were included. Data was collected on a continual basis until discontinuation of treatment with lorlatinib, death, loss to follow-up or end of study, whichever occurred first.
Duration of HCP Reported Overall Responses	21.7 Months Interval 2.0 to The upper limit of its 95% confidence interval was not estimable due to insufficient number of participants with events.

PRIMARY outcome

Timeframe: From start of lorlatinib treatment until disease progression or death or censoring date, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)

Population: All participants for whom data was collected using the data collection tool and observed in this study were included in the analysis.

PFS was derived as (date of PD or death \[by any cause in the absence of PD\] minus date of first dose of lorlatinib plus 1) divided by 30.4. Participants who had not progressed or died were censored at the date of last contact prior to the data cut-off date. PD: new soft tissue lesion (STL) detected by CT/MRI that's MIBG avid/FDG-PET avid, new STL on anatomic imaging, biopsied and confirmed as neuroblastoma (NB)/ganglioneuroblastoma (GNB), new bone site: MIBG avid/FDG-PET avid (for MIBG non-avid tumor) with CT/MRI finding consistent with tumor or confirmed histologically as NB/GNB; \>20% increase in LD as reference smallest sum on study (included baseline sum if that was the smallest on study), minimum abs increase of 5mm in sum of diameter of target STL.

Outcome measures

Outcome measures
Measure	Lorlatinib n=15 Participants Participants with ALK-aberrant neuroblastoma who initiated treatment with lorlatinib as part of an expanded access program were included. Data was collected on a continual basis until discontinuation of treatment with lorlatinib, death, loss to follow-up or end of study, whichever occurred first.
Progression Free Survival (PFS)	17.8 Months Interval 3.7 to The upper limit of its 95% confidence interval was not estimable due to insufficient number of participants with events.

PRIMARY outcome

Timeframe: From start of lorlatinib treatment until treatment stop date or censoring date, up to maximum of 36.2 months of treatment (data was retrieved and evaluated retrospectively during approximately 18 months of this study)

Population: All participants for whom data was collected using the data collection tool and observed in this study were included in the analysis.

Duration of treatment was derived as treatment stop date minus treatment start date plus 1. Participants continuing treatment at the data cut-off date were censored based on the last recorded date when the participant was known to be continuing treatment prior to the data cut-off date.

Outcome measures

Outcome measures
Measure	Lorlatinib n=15 Participants Participants with ALK-aberrant neuroblastoma who initiated treatment with lorlatinib as part of an expanded access program were included. Data was collected on a continual basis until discontinuation of treatment with lorlatinib, death, loss to follow-up or end of study, whichever occurred first.
Duration of Treatment	16.2 Months Interval 3.4 to 24.2

PRIMARY outcome

Timeframe: From date of first dose of lorlatinib until date of death or censoring date, up to maximum (max) of 36.2 months (M) of treatment (data was retrieved and evaluated retrospectively during approximately (approx.) 18 months of this study)

Population: All participants for whom data was collected using the data collection tool and observed in this study were included in the analysis.

Overall survival was derived as date of death minus treatment start date plus 1. Participants who had not died were censored at the date of last contact prior to the data cut-off date.

Outcome measures

Outcome measures
Measure	Lorlatinib n=15 Participants Participants with ALK-aberrant neuroblastoma who initiated treatment with lorlatinib as part of an expanded access program were included. Data was collected on a continual basis until discontinuation of treatment with lorlatinib, death, loss to follow-up or end of study, whichever occurred first.
Overall Survival	27.0 Months Interval 4.8 to The upper limit of its 95% confidence interval was not estimable due to insufficient number of participants with events.

PRIMARY outcome

Timeframe: From start of first dose of lorlatinib/date of informed consent(participant treated with lorlatinib) to atleast 28 day after last dose of lorlatinib to max 36.2M of treatment(data was retrieved, evaluated for approx. 18 month)

Population: All participants for whom data was collected using the data collection tool and observed in this study were included in the analysis.

An AE is any untoward medical occurrence in participants administered a medicinal product. The event need not necessarily have a causal relationship with the product treatment or usage. A SAE is any untoward medical occurrence in a participant administered a medicinal or nutritional product at any dose that: resulted in death, was life-threatening, required participant hospitalization or prolongation of hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions) and resulted in congenital anomaly/birth defect. Relatedness to treatment was determined by investigator.

Outcome measures

Outcome measures
Measure	Lorlatinib n=15 Participants Participants with ALK-aberrant neuroblastoma who initiated treatment with lorlatinib as part of an expanded access program were included. Data was collected on a continual basis until discontinuation of treatment with lorlatinib, death, loss to follow-up or end of study, whichever occurred first.
Number of Participants Reporting Adverse Events, Treatment-Related Adverse Events, Serious Adverse Events and Treatment-Related Serious-Adverse Events Treatment related AEs	14 Participants
Number of Participants Reporting Adverse Events, Treatment-Related Adverse Events, Serious Adverse Events and Treatment-Related Serious-Adverse Events Serious Treatment related AEs	3 Participants
Number of Participants Reporting Adverse Events, Treatment-Related Adverse Events, Serious Adverse Events and Treatment-Related Serious-Adverse Events AEs	14 Participants
Number of Participants Reporting Adverse Events, Treatment-Related Adverse Events, Serious Adverse Events and Treatment-Related Serious-Adverse Events Serious AEs	6 Participants

Adverse Events

Lorlatinib

Serious events: 6 serious events

Other events: 12 other events

Deaths: 8 deaths

Serious adverse events

Serious adverse events
Measure	Lorlatinib n=15 participants at risk Participants with ALK-aberrant neuroblastoma who initiated treatment with lorlatinib as part of an expanded access program were included. Data was collected on a continual basis until discontinuation of treatment with lorlatinib, death, loss to follow-up or end of study, whichever occurred first.
Nervous system disorders Hemiparesis	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Nervous system disorders Peripheral motor neuropathy	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Nervous system disorders Peripheral sensory neuropathy	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Nervous system disorders Spinal cord compression	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Infections and infestations Pneumonia	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Infections and infestations Rhinovirus infection	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Infections and infestations Sepsis	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Investigations Weight increased	13.3% 2/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Blood and lymphatic system disorders Thrombocytopenia	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Endocrine disorders Hypothyroidism	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Endocrine disorders Primary hypogonadism	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
General disorders Pyrexia	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Metabolism and nutrition disorders Hyperlipidaemia	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Renal and urinary disorders Urinary retention	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Respiratory, thoracic and mediastinal disorders Pneumonitis	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.

Other adverse events

Other adverse events
Measure	Lorlatinib n=15 participants at risk Participants with ALK-aberrant neuroblastoma who initiated treatment with lorlatinib as part of an expanded access program were included. Data was collected on a continual basis until discontinuation of treatment with lorlatinib, death, loss to follow-up or end of study, whichever occurred first.
Investigations Blood cholesterol increased	40.0% 6/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Investigations Weight increased	40.0% 6/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Investigations Alanine aminotransferase increased	20.0% 3/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Investigations Blood triglycerides increased	20.0% 3/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Investigations Aspartate aminotransferase increased	13.3% 2/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Investigations Blood lactate dehydrogenase increased	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Investigations Gamma-glutamyltransferase increased	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Investigations Lymphocyte count decreased	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Investigations Platelet count decreased	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Investigations White blood cell count decreased	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Metabolism and nutrition disorders Hypercholesterolaemia	13.3% 2/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Metabolism and nutrition disorders Hypertriglyceridaemia	13.3% 2/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Metabolism and nutrition disorders Hypokalaemia	13.3% 2/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Metabolism and nutrition disorders Hypernatraemia	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Metabolism and nutrition disorders Hyperuricaemia	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Nervous system disorders Cognitive disorder	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Nervous system disorders Fine motor delay	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Nervous system disorders Paraesthesia	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Nervous system disorders Peripheral sensory neuropathy	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Nervous system disorders Speech disorder developmental	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Blood and lymphatic system disorders Anaemia	13.3% 2/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Blood and lymphatic system disorders Thrombocytopenia	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Infections and infestations Candida infection	13.3% 2/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Infections and infestations Pyelonephritis	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Respiratory, thoracic and mediastinal disorders Epistaxis	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
General disorders Oedema peripheral	13.3% 2/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Gastrointestinal disorders Ascites	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.
Psychiatric disorders Insomnia	6.7% 1/15 • From start of first dose of lorlatinib or date of informed consent (for participants being treated with lorlatinib at study start) until at least 28 days following last administration of lorlatinib (maximum treatment duration of 36.2 months), data was retrieved and evaluated retrospectively during approx.18 months of this study An AE term may be reported as both a serious and non-serious AE but are distinct events. An AE may be serious for 1 participant and non-serious for another participant, or a participant may have experienced both a serious and non-serious episode of the same event.

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER