Clinical Trial Results:
Open label single arm Phase Ib-II study of pre-operative IPH2201 in patients with locally advanced resectable squamous cell carcinoma of the oral cavity
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Summary
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EudraCT number |
2014-002135-34 |
Trial protocol |
DE |
Global end of trial date |
26 Nov 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
25 Nov 2017
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First version publication date |
25 Nov 2017
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
IPH2201-201
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02331875 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
INNATE PHARMA
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Sponsor organisation address |
117 avenue de luminy, Marseille, France, 13009
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Public contact |
Dr Pierre Dodion, INNATE PHARMA, +33 4 30 30 30 50, pierre.dodion@innate-pharma.fr
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Scientific contact |
Dr Pierre Dodion, INNATE PHARMA, +33 4 30 30 30 50, pierre.dodion@innate-pharma.fr
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
20 Mar 2017
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
26 Nov 2016
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To evaluate the antitumor activity of pre-operative IPH2201 in patients with operable squamous cell carcinoma of the oral cavity
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Protection of trial subjects |
This study was performed in accordance with the principles stated in the Declaration of Helsinki adopted by the World Medical Association and in accordance with the International Conference of Harmonization (ICH) guidelines on Good Clinical Practice (GCP) (CPMP/ICH/135/95). The safety committee of the study was composed of The international coordinating investigator, One principal investigator per country, The director of the Charité Comprehensive Cancer Center, as Medical Oncologist with high experience in clinical tumor immunology, A medical representative of the sponsor, A radiologist. A methodologist and other principal investigators of sites which has enrolled at least one patient in the trial could join the safety committee as optional members. The safety committee had to review the data for progression and safety, for instance to decide on dose escalation. It could also be involved at any time should a major safety issue occur.
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Background therapy |
Patients should receive all necessary supportive care in the form of treatment or prophylaxis as clinically indicated e.g. transfusion of blood products, antibiotics, anti-histaminics, analgesics. No premedication was required. However, from cycle 2, premedication by acetaminophen or anti-histamine drug could be prescribed, at the investigator’s discretion, if the patient experienced any grade 1 to 3 infusion related AE at the previous cycle. | ||
Evidence for comparator |
not applicable | ||
Actual start date of recruitment |
18 Dec 2014
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Efficacy | ||
Long term follow-up duration |
2 Years | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 1
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Country: Number of subjects enrolled |
Germany: 2
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Worldwide total number of subjects |
3
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EEA total number of subjects |
3
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
1
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
Interventional Efficacy and Safety Study, Multi-center, open label single-arm phase Ib-II study including a run-in part. The first 6 patients were to received IPH2201 at a dose of 4 mg/kg q2w x 4, subsequent patients were to be treated at a dose of 10 mg/kg q2w x 4, after escalation approval by safety committee. | ||||||||||||
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Pre-assignment
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Screening details |
up to 2 weeks of screening were given to allow site to verify all selection criteria. Among the 4 patients screened, 3 were treated (1 was screen-failed at sponsor request, in the context of the premature ending of the trial). | ||||||||||||
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Period 1
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Period 1 title |
overall (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||
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Arms
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Arm title
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4mg/kg | ||||||||||||
Arm description |
only treated patients (who received at least one cycle of IPH2201) are taken in account. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
monalizumab
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Investigational medicinal product code |
IPH2201
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Other name |
NNC0141-0100, anti-NKG2A
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Pharmaceutical forms |
Powder for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
The first 6 patients were to received IPH2201 as single agent, at a dose of 4 mg/kg q2w x 4 in a 1 hour IV administration – batch IPH2201-BLDS001. IPH2201 (monalizumab) treatment period duration was of a maximum of 8 weeks. Cycle 1 administration was to be performed during the 2 weeks following the screening visit.
Administrations at cycle 2, cycle 3 and cycle 4 were performed 14 days +/- 3 after the previous cycle. One delay of up to 1 week in the treatment schedule was authorized in the absence of resolution to a grade 2 or lower of any grade ≥ 3. For a delay of more than 1 week, the investigator had to contact sponsor.
It was followed by standard treatment :
Surgical procedure: Standard Surgery to be done after the end of treatment with monalizumab, according to standard recommendations in the relevant country.
Postsurgical Adjuvant Therapy : Radiation and/ or Chemotherapy, realized after the standard surgery, according to standard recommendations in the relevant country
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Baseline characteristics reporting groups
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Reporting group title |
overall
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
4mg/kg
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Reporting group description |
only treated patients (who received at least one cycle of IPH2201) are taken in account. | ||
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End point title |
Response before surgery [1] | ||||||||||||
End point description |
Best response during treatment period
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End point type |
Primary
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End point timeframe |
up to End of Treatment visit
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The decision to stop the recruitment of patients was taken on Sept. 28, 2016, based on the low accrual rate in this trial. Thus, efficacy endpoints were analysed in a descriptive manner only, and no statistical analysis performed. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
complete response | ||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
after EOT visit
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Adverse events information
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Timeframe for reporting adverse events |
AEs were collected from consent signature date to the end of study visit.
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Adverse event reporting additional description |
after the first patient, reporting rules were changed : From the day of surgery, an event was reported if it was an SAE or if related to IPH2201 treatment (whatever grade) or has a grade ≥ 3 (irrespective of the relationship with IPH2201 treatment).
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
14.1
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Reporting groups
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Reporting group title |
4mg/kg
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Reporting group description |
only treated patients (who received at least one cycle of IPH2201) are taken in account. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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03 Jul 2015 |
- Change of the title: from “Open label single arm Phase Ib-II study of pre- operative IPH2201 in patients with resectable intermediate or high risk (stage IIIIVa) squamous cell carcinoma of the oral cavity” to “Open label single arm Phase Ib-II study of pre-operative IPH2201 in patients with locally advanced resectable squamous cell carcinoma of the oral cavity”
- Modification of inclusion criteria: the inclusion of large cT2 tumors and some stage IVB cases is now allowed:
-“Stage II with large (≥ 3 cm and≤4cm) cT2cN0cM0tumors or any cT2cN0cM0 tumor invading neighboring structures”
-“Stage IV with a primary tumor(cT)of any stage and an adenopathy assessed as cN3 considered as resectable by the investigator surgeon and no clinically or radiologically detectable metastasis”
- Modification of the exclusion criteria relative to other malignancy
- Expansion of study sites number: changed from monocentric to “up to 4 sites located in Germany” |
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15 Oct 2015 |
- Expansion of study sites number: changed from “up to 4 sites located in Germany” to “Approximately 12 sites in Europe”
- Expansion of study duration: LPLV changed from December 2017 to June 2018
-Change in contraception requirements during the study: male and female patients must use a highly effective contraception method throughout the study and up to 5 months after treatment discontinuation (previously up to 16 weeks). Pregnancy reporting rules have also been updated consequently.
- New reporting rules for AEs: “From the day of surgery, an event was reported if it was an SAE or if related to IPH2201 treatment (whatever grade) or has a grade ≥ 3 (irrespective of the relationship with IPH2201 treatment)“.
-New reporting rules for concomitant medications: “All concomitant medications given to a patient prior to surgery are to be reported. From the surgery day, a concomitant treatment has to be reported if it is corticosteroid, or given to treat a AE (as defined above) or a condition described in medical history”
- Change of safety committee member list, to include one principal investigator per country, other principal investigator and other principal investigator of sites which have enrolled at least one patient in the trial) |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
| Overall, the limited number of patients treated in this study does not allow concluding on primary and secondary objectives. Efficacy endpoints were analysed in a descriptive manner only, and no statistical analysis performed. | |||||||
