Trial Outcomes & Findings for IGF Inhibition With Xentuzumab Prior to Radical Prostatectomy (NCT NCT05110495)

Last Updated: 2025-02-17

Results Overview

Diagnostic biopsies (pre-treatment) and in-theatre cores (post-treatment) were stained with phospho-IGF-1R. Percentage of positively stained tumour cells in each sample were compared and the percentage change between timepoints was quantified. A negative percentage change indicates a reduction in phospho-IGF-1R in post-treatment samples. This endpoint was designed to assess the amount of IGF pathway inhibition induced by xentuzumab.

Recruitment status

COMPLETED

Study phase

EARLY_PHASE1

Target enrollment

27 participants

Primary outcome timeframe

From first xentuzumab infusion at week 1 (pre-treatment) to surgery at week 4-13 (post-treatment). Up to 13 weeks total.

Results posted on

2025-02-17

Participant Flow

Participant milestones

Participant milestones
Measure	Xentuzumab All patients will be allocated to receive Xentuzumab Xentuzumab: The study IMP is xentuzumab, a humanised IgG1 monoclonal antibody that neutralises the IGF ligands to inhibit activation of IGF-1R and INSR-A, suppressing IGF-mediated proliferation, invasion and therapy resistance
Overall Study STARTED	27
Overall Study COMPLETED	25
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Xentuzumab All patients will be allocated to receive Xentuzumab Xentuzumab: The study IMP is xentuzumab, a humanised IgG1 monoclonal antibody that neutralises the IGF ligands to inhibit activation of IGF-1R and INSR-A, suppressing IGF-mediated proliferation, invasion and therapy resistance
Overall Study Lost to Follow-up	1
Overall Study Completed treatment with IMP but disease progressed prior to surgery.	1

Baseline Characteristics

IGF Inhibition With Xentuzumab Prior to Radical Prostatectomy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Xentuzumab n=27 Participants All patients will be allocated to receive Xentuzumab Xentuzumab: The study IMP is xentuzumab, a humanised IgG1 monoclonal antibody that neutralises the IGF ligands to inhibit activation of IGF-1R and INSR-A, suppressing IGF-mediated proliferation, invasion and therapy resistance
Region of Enrollment United Kingdom	27 participants n=99 Participants
Age, Continuous	66 years n=99 Participants
Sex: Female, Male Female	0 Participants n=99 Participants
Sex: Female, Male Male	27 Participants n=99 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	27 Participants n=99 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants

PRIMARY outcome

Timeframe: From first xentuzumab infusion at week 1 (pre-treatment) to surgery at week 4-13 (post-treatment). Up to 13 weeks total.

Population: Units given accounts for a pre-treatment and post-treatment sample per participant. Number analysed excludes samples from 6 participants that were missing either the pre-treatment or post-treatment sample, or could not be analysed for other reasons.

Outcome measures

Outcome measures
Measure	Xentuzumab n=42 Tissue samples All patients will be allocated to receive Xentuzumab Xentuzumab: The study IMP is xentuzumab, a humanised IgG1 monoclonal antibody that neutralises the IGF ligands to inhibit activation of IGF-1R and INSR-A, suppressing IGF-mediated proliferation, invasion and therapy resistance
Percentage Change of Phospho-IGF-1R Positive Tumour Cells Following Treatment With Xentuzumab	-8.28 Percentage change Phospho-IGF-1R+ cells Interval -97.94 to 481.68

PRIMARY outcome

Timeframe: From first xentuzumab infusion at week 1 (pre-treatment) to surgery at week 4-13 (post-treatment). Up to 13 weeks total.

Population: Units analysed describes pre-treatment and post-treatment sample for each participant. Number analysed excludes 10 participants that were missing either the pre-treatment or post-treatment sample, or could not be analysed for other reasons.

Diagnostic biopsies (pre-treatment) and in-theatre cores (post-treatment) were stained by phospho-S6. Percentage of positively stained tumour cells in each sample were compared and the percentage change between timepoints was quantified. A negative percentage change indicates a reduction in phospho-S6 in post-treatment samples. This endpoint was designed to assess the amount of IGF pathway inhibition induced by xentuzumab.

Outcome measures

Outcome measures
Measure	Xentuzumab n=34 Tissue samples All patients will be allocated to receive Xentuzumab Xentuzumab: The study IMP is xentuzumab, a humanised IgG1 monoclonal antibody that neutralises the IGF ligands to inhibit activation of IGF-1R and INSR-A, suppressing IGF-mediated proliferation, invasion and therapy resistance
Percentage Change of Phospho-S6 Positive Tumour Cells Following Treatment With Xentuzumab	-52.55 Percentage change of Phospho-S6+ cells Interval -87.61 to 60.11

SECONDARY outcome

Timeframe: From first xentuzumab infusion at week 1 (pre-treatment) to surgery at week 4-13 (post-treatment). Up to 13 weeks total.

Population: Total number of participants who had at least 4 doses of xentuzumab. Excludes one registered patient who progressed prior to surgery and came off trial.

This endpoint was a measure of feasibility of the treatment schedule in the pre-operative setting.

Outcome measures

Outcome measures
Measure	Xentuzumab n=26 Participants All patients will be allocated to receive Xentuzumab Xentuzumab: The study IMP is xentuzumab, a humanised IgG1 monoclonal antibody that neutralises the IGF ligands to inhibit activation of IGF-1R and INSR-A, suppressing IGF-mediated proliferation, invasion and therapy resistance
Number of Participants Who Had at Least 4 Doses of Xentuzumab and Proceeded to Have Surgery Per the Protocol Schedule Surgery performed on schedule	26 Participants
Number of Participants Who Had at Least 4 Doses of Xentuzumab and Proceeded to Have Surgery Per the Protocol Schedule Surgery delayed by trial treatment	0 Participants

SECONDARY outcome

Timeframe: From first xentuzumab infusion at week 1 (pre-treatment) to surgery at week 4-13 (post-treatment). Up to 13 weeks total.

Population: Number of participants who had more than 4 Doses of xentuzumab.

All participants who had more than 4 doses of xentuzumab were considered to have had their surgery delayed by factors other than trial treatment. Per protocol, all participants who had delayed surgery received additional weekly doses of xentuzumab. Reason for delay was not recorded as part of the study dataset. This endpoint was a measure of feasibility of the treatment schedule in the pre-operative setting.

Outcome measures

Outcome measures
Measure	Xentuzumab n=15 Participants All patients will be allocated to receive Xentuzumab Xentuzumab: The study IMP is xentuzumab, a humanised IgG1 monoclonal antibody that neutralises the IGF ligands to inhibit activation of IGF-1R and INSR-A, suppressing IGF-mediated proliferation, invasion and therapy resistance
Median Delay in Surgery in Participants Who Had More Than 4 Doses of Xentuzumab (and Whose Surgery Was Delayed by Factors Other Than Trial Treatment)	2 weeks Interval 2.0 to 9.0

SECONDARY outcome

Timeframe: From consent at week -1 to the end of study visit at up to 19 weeks

Population: All participants registered to take part in the WINGMEN trial. All participants received xentuzumab.

This endpoint was designed to assess safety and tolerability of xentuzumab administered in the pre-prostatectomy setting. AEs \& SAEs were graded using CTCAE v5.0, with higher grades considered to be worse outcomes.

Outcome measures

Outcome measures
Measure	Xentuzumab n=27 Participants All patients will be allocated to receive Xentuzumab Xentuzumab: The study IMP is xentuzumab, a humanised IgG1 monoclonal antibody that neutralises the IGF ligands to inhibit activation of IGF-1R and INSR-A, suppressing IGF-mediated proliferation, invasion and therapy resistance
Number of Patients Experiencing an Adverse Event (AE) or Serious Adverse Event (SAE) While On-trial Any AE, Highest Grade 1 or 2 (CTCAE v5.0)	23 Participants
Number of Patients Experiencing an Adverse Event (AE) or Serious Adverse Event (SAE) While On-trial Any AE, Highest Grade 3,4,5 (CTCAE v5.0)	1 Participants
Number of Patients Experiencing an Adverse Event (AE) or Serious Adverse Event (SAE) While On-trial Any SAE, Highest Grade 1 or 2 (CTCAE v5.0)	0 Participants
Number of Patients Experiencing an Adverse Event (AE) or Serious Adverse Event (SAE) While On-trial Any SAE, Highest Grade 3,4,5 (CTCAE v5.0)	0 Participants
Number of Patients Experiencing an Adverse Event (AE) or Serious Adverse Event (SAE) While On-trial No AEs or SAEs reported	3 Participants

SECONDARY outcome

Timeframe: From consent at week -1 to the end of study visit at up to 19 weeks

Population: All participants registered to take part in the WINGMEN trial. All participants received xentuzumab.

Number of patients with any TRAE from the time of consent to the end of study visit. TRAEs are AEs that are investigator-determined to be definitely, probably or possibly related to treatment with xentuzumab and graded using CTCAE v5.0, with higher grades considered to be worse outcomes. This endpoint was designed to assess safety and tolerability of xentuzumab administered in the pre-prostatectomy setting.

Outcome measures

Outcome measures
Measure	Xentuzumab n=27 Participants All patients will be allocated to receive Xentuzumab Xentuzumab: The study IMP is xentuzumab, a humanised IgG1 monoclonal antibody that neutralises the IGF ligands to inhibit activation of IGF-1R and INSR-A, suppressing IGF-mediated proliferation, invasion and therapy resistance
Number of Patients With Any Adverse Event Assessed as Treatment-Related (TRAE) While On-trial Any TRAE, Highest Grade 1 or 2 (CTCAE v5.0)	17 Participants
Number of Patients With Any Adverse Event Assessed as Treatment-Related (TRAE) While On-trial Any TRAE, Highest Grade 3,4,5 (CTCAE v5.0)	0 Participants
Number of Patients With Any Adverse Event Assessed as Treatment-Related (TRAE) While On-trial No TRAE	10 Participants

Adverse Events

Xentuzumab

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Xentuzumab n=27 participants at risk All patients were allocated to receive the study IMP, Xentuzumab. Xentuzumab is a humanised IgG1 monoclonal antibody that neutralises the IGF ligands to inhibit activation of IGF-1R and INSR-A, suppressing IGF-mediated proliferation, invasion and therapy resistance.
Blood and lymphatic system disorders Blood & Lymphatic System Disorders	18.5% 5/27 • Number of events 10 • From consent to end of study visit (up to 19 weeks). Adverse Event data was collected during trial visits from investigator-led assessments as specified in the protocol.
Eye disorders Eye disorders	3.7% 1/27 • Number of events 1 • From consent to end of study visit (up to 19 weeks). Adverse Event data was collected during trial visits from investigator-led assessments as specified in the protocol.
Gastrointestinal disorders Gastrointestinal Disorders	29.6% 8/27 • Number of events 12 • From consent to end of study visit (up to 19 weeks). Adverse Event data was collected during trial visits from investigator-led assessments as specified in the protocol.
General disorders General Disorders & Administration Site Conditions	40.7% 11/27 • Number of events 15 • From consent to end of study visit (up to 19 weeks). Adverse Event data was collected during trial visits from investigator-led assessments as specified in the protocol.
Infections and infestations Infections & Infestations	18.5% 5/27 • Number of events 6 • From consent to end of study visit (up to 19 weeks). Adverse Event data was collected during trial visits from investigator-led assessments as specified in the protocol.
Injury, poisoning and procedural complications Injury; poisoning and procedural complications	11.1% 3/27 • Number of events 3 • From consent to end of study visit (up to 19 weeks). Adverse Event data was collected during trial visits from investigator-led assessments as specified in the protocol.
Metabolism and nutrition disorders Metabolism & Nutrition Disorders	14.8% 4/27 • Number of events 5 • From consent to end of study visit (up to 19 weeks). Adverse Event data was collected during trial visits from investigator-led assessments as specified in the protocol.
Musculoskeletal and connective tissue disorders Musculoskeletal & Connective Tissue Disorders	25.9% 7/27 • Number of events 7 • From consent to end of study visit (up to 19 weeks). Adverse Event data was collected during trial visits from investigator-led assessments as specified in the protocol.
Nervous system disorders Nervous System Disorders	22.2% 6/27 • Number of events 8 • From consent to end of study visit (up to 19 weeks). Adverse Event data was collected during trial visits from investigator-led assessments as specified in the protocol.
Renal and urinary disorders Renal and urinary disorders	40.7% 11/27 • Number of events 13 • From consent to end of study visit (up to 19 weeks). Adverse Event data was collected during trial visits from investigator-led assessments as specified in the protocol.
Reproductive system and breast disorders Reproductive system and breast disorders	11.1% 3/27 • Number of events 3 • From consent to end of study visit (up to 19 weeks). Adverse Event data was collected during trial visits from investigator-led assessments as specified in the protocol.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	7.4% 2/27 • Number of events 2 • From consent to end of study visit (up to 19 weeks). Adverse Event data was collected during trial visits from investigator-led assessments as specified in the protocol.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	7.4% 2/27 • Number of events 2 • From consent to end of study visit (up to 19 weeks). Adverse Event data was collected during trial visits from investigator-led assessments as specified in the protocol.
Surgical and medical procedures Surgical and medical procedures	11.1% 3/27 • Number of events 3 • From consent to end of study visit (up to 19 weeks). Adverse Event data was collected during trial visits from investigator-led assessments as specified in the protocol.
Vascular disorders Vascular disorders	11.1% 3/27 • Number of events 6 • From consent to end of study visit (up to 19 weeks). Adverse Event data was collected during trial visits from investigator-led assessments as specified in the protocol.

Additional Information

Dr Simon Lord

University of Oxford

Phone: 01865 227212

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place