Trial Outcomes & Findings for Phase 3 Study of Futuximab/Modotuximab in Combination With Trifluridine/Tipiracil Versus Trifluridine/Tipiracil Single Agent in Participants With Previously Treated Metastatic Colorectal Cancer (NCT NCT05223673)
NCT ID: NCT05223673
Last Updated: 2024-08-20
Results Overview
DLTs observed during a 28-day period. A DLT is defined as the following: A clinically significant AE graded according to the NCI-CTCAE version 5.0, observed during the initial 28- day treatment period following the first IMP administration. Assessed as unrelated to underlying disease, disease progression, intercurrent illness, or concomitant medications. At least possibly related to the IMPs (futuximab/modotuximab or trifluridine/tipiracil or both) by the investigator and meeting criteria as outlined in the protocol.
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
7 participants
Primary outcome timeframe
End of cycle 1 (Each cycle is up to 28 days)
Results posted on
2024-08-20
Participant Flow
Sponsor decided to discontinue the study during the Lead-In part and the Phase III (randomized) part was not started due to strategic reasons.
Participant milestones
| Measure |
Futuximab/Modotuximab Combined With Trifluridine/Tipiracil (Safety Lead-In and Phase III Parts)
Futuximab/modotuximab: Concentrate for solution for infusion, futuximab/modotuximab was administered via IV route, once weekly of each cycle at 9 mg/kg/dose at Cycle 1 Day 1 and then at 6 mg/kg/dose. Each cycle is up to 28 days.
Trifluridine/Tipiracil: Film-coated tablets of trifluridine/tipiracil (35 mg/m²/dose) was administered orally before futuximab/ modotuximab administration, twice a day (BID) within 1 hour after completion of morning and evening meals, 5 days on/2 days off, over 14 days, followed by a 14-day rest. This treatment cycle was repeated every 28 days.
|
|---|---|
|
Overall Study
STARTED
|
7
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
7
|
Reasons for withdrawal
| Measure |
Futuximab/Modotuximab Combined With Trifluridine/Tipiracil (Safety Lead-In and Phase III Parts)
Futuximab/modotuximab: Concentrate for solution for infusion, futuximab/modotuximab was administered via IV route, once weekly of each cycle at 9 mg/kg/dose at Cycle 1 Day 1 and then at 6 mg/kg/dose. Each cycle is up to 28 days.
Trifluridine/Tipiracil: Film-coated tablets of trifluridine/tipiracil (35 mg/m²/dose) was administered orally before futuximab/ modotuximab administration, twice a day (BID) within 1 hour after completion of morning and evening meals, 5 days on/2 days off, over 14 days, followed by a 14-day rest. This treatment cycle was repeated every 28 days.
|
|---|---|
|
Overall Study
Protocol Violation
|
1
|
|
Overall Study
Study termination
|
6
|
Baseline Characteristics
Phase 3 Study of Futuximab/Modotuximab in Combination With Trifluridine/Tipiracil Versus Trifluridine/Tipiracil Single Agent in Participants With Previously Treated Metastatic Colorectal Cancer
Baseline characteristics by cohort
| Measure |
Futuximab/Modotuximab Combined With Trifluridine/Tipiracil (Safety Lead-In and Phase III Parts)
n=7 Participants
Futuximab/modotuximab: Concentrate for solution for infusion, futuximab/modotuximab was administered via IV route, once weekly of each cycle at 9 mg/kg/dose at Cycle 1 Day 1 and then at 6 mg/kg/dose. Each cycle is up to 28 days.
Trifluridine/Tipiracil: Film-coated tablets of trifluridine/tipiracil (35 mg/m²/dose) was administered orally before futuximab/ modotuximab administration, twice a day (BID) within 1 hour after completion of morning and evening meals, 5 days on/2 days off, over 14 days, followed by a 14-day rest. This treatment cycle was repeated every 28 days.
|
|---|---|
|
Age, Continuous
|
67.3 years
STANDARD_DEVIATION 3.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · White
|
6 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race · Asian
|
1 Participants
n=5 Participants
|
|
Primary tumour site
Rectosigmoid segment
|
2 Participants
n=5 Participants
|
|
Primary tumour site
Rectum
|
4 Participants
n=5 Participants
|
|
Primary tumour site
Sigmoid colon
|
1 Participants
n=5 Participants
|
|
Site of metastasis
Liver
|
5 Participants
n=5 Participants
|
|
Site of metastasis
Lung
|
6 Participants
n=5 Participants
|
|
Site of metastasis
Distant lymph node
|
3 Participants
n=5 Participants
|
|
Site of metastasis
Bone
|
1 Participants
n=5 Participants
|
|
Site of metastasis
Other
|
2 Participants
n=5 Participants
|
|
Disease duration (years)
|
4.062 years
STANDARD_DEVIATION 2.630 • n=5 Participants
|
|
Time from first metastasis diagnosis to inclusion (months)
|
37.784 months
STANDARD_DEVIATION 22.556 • n=5 Participants
|
PRIMARY outcome
Timeframe: End of cycle 1 (Each cycle is up to 28 days)DLTs observed during a 28-day period. A DLT is defined as the following: A clinically significant AE graded according to the NCI-CTCAE version 5.0, observed during the initial 28- day treatment period following the first IMP administration. Assessed as unrelated to underlying disease, disease progression, intercurrent illness, or concomitant medications. At least possibly related to the IMPs (futuximab/modotuximab or trifluridine/tipiracil or both) by the investigator and meeting criteria as outlined in the protocol.
Outcome measures
| Measure |
Futuximab/Modotuximab Combined With Trifluridine/Tipiracil (Safety Lead-In and Phase III Parts)
n=7 Participants
Futuximab/modotuximab: Concentrate for solution for infusion, futuximab/modotuximab was administered via IV route, once weekly of each cycle at 9 mg/kg/dose at Cycle 1 Day 1 and then at 6 mg/kg/dose. Each cycle is up to 28 days.
Trifluridine/Tipiracil: Film-coated tablets of trifluridine/tipiracil (35 mg/m²/dose) was administered orally before futuximab/ modotuximab administration, twice a day (BID) within 1 hour after completion of morning and evening meals, 5 days on/2 days off, over 14 days, followed by a 14-day rest. This treatment cycle was repeated every 28 days.
|
|---|---|
|
Incidence of Dose-limiting Toxicities (DLTs) (Safety Lead-In Part)
|
0 dose-limiting toxicities (DLTs)
|
PRIMARY outcome
Timeframe: up to 4 years 9 monthsPopulation: Sponsor decided to discontinue the study during the Lead-In part and the Phase III part was not started due to strategic reasons. Therefore, outcome measure data is not available
Time elapsed from date of randomization until the date of death from any cause
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: up to 24 monthsPopulation: No analysis done for this outcome measure as data was not collected.
Time elapsed from the first IMP intake to death
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: up to 4 years 9 monthsPopulation: Sponsor decided to discontinue the study during the Lead-In part and the Phase III part was not started due to strategic reasons. Therefore, outcome measure data is not available
Time elapsed from the date of randomization into the study to disease progression/death
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: up to 4 years 9 monthsPopulation: Sponsor decided to discontinue the study during the Lead-In part and the Phase III part was not started due to strategic reasons. Therefore, outcome measure data is not available
Time elapsed from the date of randomization into the study to disease progression/death
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Through study completion, up to 4 years 9 monthsPopulation: Sponsor decided to discontinue the study during the Lead-In part and the Phase III part was not started due to strategic reasons. Therefore, outcome measure data is not available
Incidence, severity, and relationship of treatment emergent adverse event and treatment emergent serious adverse event
Outcome measures
Outcome data not reported
Adverse Events
Futuximab/Modotuximab Combined With Trifluridine/Tipiracil (Safety Lead-In and Phase III Parts)
Serious events: 3 serious events
Other events: 7 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Futuximab/Modotuximab Combined With Trifluridine/Tipiracil (Safety Lead-In and Phase III Parts)
n=7 participants at risk
Futuximab/modotuximab: Concentrate for solution for infusion, futuximab/modotuximab was administered via IV route, once weekly of each cycle at 9 mg/kg/dose at Cycle 1 Day 1 and then at 6 mg/kg/dose. Each cycle is up to 28 days.
Trifluridine/Tipiracil: Film-coated tablets of trifluridine/tipiracil (35 mg/m²/dose) was administered orally before futuximab/ modotuximab administration, twice a day (BID) within 1 hour after completion of morning and evening meals, 5 days on/2 days off, over 14 days, followed by a 14-day rest. This treatment cycle was repeated every 28 days.
|
|---|---|
|
Ear and labyrinth disorders
Vertigo
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Hepatobiliary disorders
Cholecystitis acute
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Hepatobiliary disorders
Jaundice
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Infections and infestations
Pneumonia bacterial
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Infections and infestations
Sepsis
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Investigations
Blood creatinine increased
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Respiratory, thoracic and mediastinal disorders
Hyperventilation
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
Other adverse events
| Measure |
Futuximab/Modotuximab Combined With Trifluridine/Tipiracil (Safety Lead-In and Phase III Parts)
n=7 participants at risk
Futuximab/modotuximab: Concentrate for solution for infusion, futuximab/modotuximab was administered via IV route, once weekly of each cycle at 9 mg/kg/dose at Cycle 1 Day 1 and then at 6 mg/kg/dose. Each cycle is up to 28 days.
Trifluridine/Tipiracil: Film-coated tablets of trifluridine/tipiracil (35 mg/m²/dose) was administered orally before futuximab/ modotuximab administration, twice a day (BID) within 1 hour after completion of morning and evening meals, 5 days on/2 days off, over 14 days, followed by a 14-day rest. This treatment cycle was repeated every 28 days.
|
|---|---|
|
Blood and lymphatic system disorders
Eosinophilia
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Blood and lymphatic system disorders
Leukocytosis
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Blood and lymphatic system disorders
Neutropenia
|
71.4%
5/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Blood and lymphatic system disorders
Neutrophilia
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Ear and labyrinth disorders
Tympanic membrane perforation
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Gastrointestinal disorders
Abdominal pain
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Gastrointestinal disorders
Constipation
|
28.6%
2/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Gastrointestinal disorders
Diarrhoea
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Gastrointestinal disorders
Dry mouth
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Gastrointestinal disorders
Haematochezia
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Gastrointestinal disorders
Nausea
|
42.9%
3/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Gastrointestinal disorders
Stomatitis
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Gastrointestinal disorders
Vomiting
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
General disorders
Asthenia
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
General disorders
Device related thrombosis
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
General disorders
Fatigue
|
57.1%
4/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
General disorders
Influenza like illness
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
General disorders
Oedema peripheral
|
28.6%
2/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
General disorders
Pyrexia
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Infections and infestations
COVID-19
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Infections and infestations
Ear infection
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Infections and infestations
Influenza
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Infections and infestations
Otitis externa
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Infections and infestations
Paronychia
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Infections and infestations
Tinea pedis
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Infections and infestations
Upper respiratory tract infection
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Injury, poisoning and procedural complications
Fall
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
57.1%
4/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Investigations
Alanine aminotransferase increased
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Investigations
Creatinine renal clearance decreased
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Investigations
White blood cell count decreased
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
42.9%
3/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
28.6%
2/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
71.4%
5/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Musculoskeletal and connective tissue disorders
Sacral pain
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Nervous system disorders
Aphasia
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Nervous system disorders
Dizziness
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Nervous system disorders
Dysgeusia
|
28.6%
2/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Nervous system disorders
Taste disorder
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Psychiatric disorders
Confusional state
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Renal and urinary disorders
Nocturia
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Renal and urinary disorders
Proteinuria
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Skin and subcutaneous tissue disorders
Acne
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
85.7%
6/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
71.4%
5/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Skin and subcutaneous tissue disorders
Erythema
|
28.6%
2/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Skin and subcutaneous tissue disorders
Onychoclasis
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
28.6%
2/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
|
Vascular disorders
Orthostatic hypotension
|
14.3%
1/7 • Any AEs reported from the date of the first administration of IMP to 30 days after the last date of IMP administration (approximately 2 months)
|
Additional Information
Clinical Studies Department
Institut de Recherches Internationales Servier (I.R.I.S.)
Phone: +33 1 55 72 60 00
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place