Clinical Trial Results:
A Phase 2, Open-Label, Multi-cohort Study of PD-L1 Probody™ Therapeutic CX-072 in Combination With Other Anticancer Therapy in Adults With Solid Tumors (PROCLAIM-CX-072-002)
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Summary
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EudraCT number |
2019-000999-42 |
Trial protocol |
GB ES NL |
Global end of trial date |
21 May 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Aug 2021
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First version publication date |
06 Aug 2021
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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 |
CTMX-M-072-002
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03993379 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
IND: 142922 | ||
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Sponsors
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Sponsor organisation name |
CytomX Therapeutics, Inc.
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Sponsor organisation address |
151 Oyster Point Boulevard Suite 400, South San Francisco, United States, CA 94080-1913
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Public contact |
Clinical Trial Team, CytomX Therapeutics, Inc. , +1 (650) 515-3185, Clinicaltrials@cytomx.com
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Scientific contact |
Clinical Trial Team, CytomX Therapeutics, Inc. , +1 (650) 515-3185, Clinicaltrials@cytomx.com
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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 |
27 Jul 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
21 May 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
21 May 2020
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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 |
Part A:
• To obtain evidence of antitumor effect of CX-072 in combination with ipilimumab in subjects with solid tumors based on the objective response rate (ORR) as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Part B:
• To obtain evidence of antitumor effect of CX-072 in combination with ipilimumab in subjects with solid tumors based on the pathologic response following neoadjuvant administration of combination treatment
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Protection of trial subjects |
This study was conducted in accordance with the clinical protocol as approved by the applicable Institutional Review Board/Independent Ethics Committee, International Council for Harmonisation Good Clinical Practice Guidelines, and other applicable regulatory requirements.
The informed consent form (ICF) was explained to the subjects for the risks and benefits of study participation in simple terms before they entered into the study. Each subject signed an ICF containing appropriate study and study drug information and was provided a copy of the ICF.
Appropriate study restrictions based on the mechanism of action of CX-072 (i.e., targeting the programmed death 1 [PD-1]/programmed death-ligand 1 [PD-L1] pathway) were implemented including screening procedures and exclusion criteria to ensure the safety of subjects.
Proper instruction regarding adverse events (AEs) of special interest was provided to each site to ensure prompt reporting and communication between the Sponsor, Investigators, and the applicable regulatory agencies or health authorities. Individual subject safety was assessed by the Investigator on an ongoing basis during the study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
20 Nov 2019
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Long term follow-up planned |
No
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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 |
United States: 3
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Worldwide total number of subjects |
3
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EEA total number of subjects |
0
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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 |
1
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85 years and over |
1
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Recruitment
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Recruitment details |
This is a Phase 2, multicenter, global, open-label, multi-cohort, and parallel-cohort study. This study was composed of 2 parts (Part A and Part B) and 4 cohorts (Cohorts A1, A2, A3, and B1). Enrollment into each cohort was to occur in parallel and in 2 stages for all cohorts of Part A and Part B. | ||||||||||||
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Pre-assignment
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Screening details |
A total of 3 subjects were enrolled into Cohort A2 of the study. The study was terminated early after these 3 subjects were enrolled. Only Cohort A2 is represented in this summary because all other study cohorts (A1, A3, and B1) did not enroll any subjects. | ||||||||||||
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Period 1
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Period 1 title |
Overall study (Part A [Cohort A2]) (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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Cohort A2 | ||||||||||||
Arm description |
Subjects with histologically or cytologically confirmed Stage III (unresectable) or Stage IV melanoma who had experienced progressive disease or relapse following treatment with a PD-1/PD-L1 immune checkpoint inhibitor received CX-072 in combination with ipilimumab in Cohort A2. Subjects were to be treated with 4 doses of combination therapy (intravenous infusion of 800 mg CX-072 plus 3 mg/kg ipilimumab) once every 3 weeks and then with 800 mg CX-072 intravenous monotherapy once every 2 weeks after the 3 weeks of the fourth dose of combination therapy until the occurrence of progressive disease by immune-related RECIST (irRECIST), unacceptable toxicity, or the subjects met any other criterion for treatment discontinuation. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
CX-072
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous drip use
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Dosage and administration details |
CX-072 was supplied as a sterile solution for intravenous administration in a 10 mL volume, and each vial contained 100 mg of CX-072 formulated with suitable compendial excipients.
In combination therapy, CX-072 was administered first, followed by a saline flush, and then followed by the ipilimumab infusion. During monotherapy, 800 mg CX-072 was infused over 60 minutes.
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Investigational medicinal product name |
Ipilimumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous drip use
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Dosage and administration details |
Ipilimumab was supplied as a sterile, preservative-free solution in 10 mL (50 mg) and 40 mL (200 mg) vials at a concentration of 5 mg/mL. Ipilimumab dosing was based on the subject’s weight and dose level assignment. Ipilimumab could be diluted with 0.9% sodium chloride injection, United States Pharmacopoeia (USP) or 5% Dextrose Injection, USP to a final concentration ranging from 1 to 2 mg/mL.
Ipilimumab (3 mg/kg) was administered as a 90-minute intravenous infusion and was infused no sooner than 30 minutes after completion of the CX-072 infusion.
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Baseline characteristics reporting groups
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Reporting group title |
Cohort A2
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Reporting group description |
Subjects with histologically or cytologically confirmed Stage III (unresectable) or Stage IV melanoma who had experienced progressive disease or relapse following treatment with a PD-1/PD-L1 immune checkpoint inhibitor received CX-072 in combination with ipilimumab in Cohort A2. Subjects were to be treated with 4 doses of combination therapy (intravenous infusion of 800 mg CX-072 plus 3 mg/kg ipilimumab) once every 3 weeks and then with 800 mg CX-072 intravenous monotherapy once every 2 weeks after the 3 weeks of the fourth dose of combination therapy until the occurrence of progressive disease by immune-related RECIST (irRECIST), unacceptable toxicity, or the subjects met any other criterion for treatment discontinuation. | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Cohort A2
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Reporting group description |
Subjects with histologically or cytologically confirmed Stage III (unresectable) or Stage IV melanoma who had experienced progressive disease or relapse following treatment with a PD-1/PD-L1 immune checkpoint inhibitor received CX-072 in combination with ipilimumab in Cohort A2. Subjects were to be treated with 4 doses of combination therapy (intravenous infusion of 800 mg CX-072 plus 3 mg/kg ipilimumab) once every 3 weeks and then with 800 mg CX-072 intravenous monotherapy once every 2 weeks after the 3 weeks of the fourth dose of combination therapy until the occurrence of progressive disease by immune-related RECIST (irRECIST), unacceptable toxicity, or the subjects met any other criterion for treatment discontinuation. | ||
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End point title |
Number of subjects with ORR by the RECIST v1.1 [1] | ||||||
End point description |
For solid tumors, response evaluation is based upon RECIST criteria (v1.1) and ORR was defined as the proportion of subjects with complete response (CR) or partial response (PR) on 2 consecutive tumor assessments at least 4 weeks apart according to RECIST (RECIST v1.1). However, after enrollment of 3 subjects, the study was terminated at the Sponsor's discretion. Descriptive statistical summaries were produced.
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End point type |
Primary
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End point timeframe |
Not applicable
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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: Data tabulations and summaries were performed, but no formal statistical analyses were undertaken due to early study termination. With 3 subjects enrolled, there was insufficient subject data to determine stable estimates for any of the proposed efficacy study endpoints. Additionally, pharmacokinetic analyses were not performed. |
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| Notes [2] - Due to early termination, efficacy analyses were not performed. |
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| No statistical analyses for this end point | |||||||
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End point title |
Numbers of subjects experiencing antitumor activity by irRECIST | ||||||
End point description |
Antitumor activity was to be evaluated in the subjects with solid tumors treated with CX-072 in combination with ipilimumab based on ORR by irRECIST. However, after enrollment of 3 subjects, the study was terminated at the Sponsor's discretion. Descriptive statistical summaries were produced.
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End point type |
Secondary
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End point timeframe |
Not applicable
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| Notes [3] - Due to early termination, efficacy analyses were not performed. |
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| No statistical analyses for this end point | |||||||
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Adverse events information
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Timeframe for reporting adverse events |
AEs occurring after the ICF was signed and up to 30 days after the last dose of the study drug were reported.
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Adverse event reporting additional description |
Subjects were continued to be monitored for immune-related AEs, AEs ≥ Grade 3, and serious AEs (SAEs) up to 90 days following their last dose of the study drug. All the treatment-emergent adverse events reported during the study are provided here for the enrolled subjects.
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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 |
22.0
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Reporting groups
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Reporting group title |
Cohort A2
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Reporting group description |
Safety assessments included all 3 subjects who were enrolled in Cohort A2 and received at least one dose of the study drug. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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24 May 2019 |
No subject enrolled in the study under Amendment 1 (24 May 2019) of the protocol. Major changes to the conduct of the study implemented with Amendment 1 were as follows:
• Further defined the patient population in Cohort A2 who experienced disease progression during treatment with an anti-PD-1/PD-L1 antibody to include the time since last progression, progression criteria, and minimum number of cycles
• Revised to routinely collect SAEs and Grade 3 and 4 AEs up to 90 days after the last dose of study treatment
• Instructed investigators to follow the CX-072 Module if/when there were overlapping directives between the Module and Common Core |
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21 Aug 2019 |
All 3 subjects were enrolled in the study under Amendment 2 (21 August 2019) of the protocol. Major changes to the conduct of the study implemented with Amendment 2 were as follows:
• Specified the terms and planned number of enrollment into study Part A, Cohort A2, under a Simon’s 2-Stage design, so that for Amendment 2, only Stage 1 of Cohort A2 was included with an accompanying rationale for change in statistical assumptions for that cohort
• Revised the eligibility criteria for the study and updated dose modification details for select adverse events (such as myasthenia gravis or Guillain-Barré syndrome and hypothyroidism or hyperthyroidism)
• Revised the biomarker/antidrug antibody serum sample time for predose, study treatment days, and at the end of treatment visit
• Updated reference safety information based on local ipilimumab package insert.
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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. | |||||||
| No formal statistical analyses were undertaken due to early study termination. There was insufficient subject data (3 subjects enrolled) to determine stable estimates for any of the proposed study endpoints. Pharmacokinetic analyses were not done. | |||||||
