Solid Tumors and LymphomasPhase 1NCT03172936
Study of the Safety and Efficacy of MIW815 With PDR001 in Patients With Advanced/Metastatic Solid Tumors or Lymphomas
A Phase 1 study testing MIW815 and PDR001 in people with Solid Tumors and Lymphomas, run by Novartis Pharmaceuticals at 12 sites in 8 countries.
Trial summary
The purpose of this study was to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics and antitumor activity of MIW815 (ADU-S100) in combination with PDR001. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors and Lymphomas
- What is being tested?
- MIW815 and PDR001
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 106 participants
- Where
- 12 sitesin 8 countries
- Study dates
- 8 Sep 2017to 18 Dec 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ECOG ≤ 1 Willing to undergo tumor biopsies from injected and distal lesions
- Must have two biopsy accessible lesions:
Who cannot join
- Symptomatic or untreated leptomeningeal disease. Presence of symptomatic central nervous system metastases Impaired cardiac function or clinically significant cardiac disease Active autoimmune disease or a documented history of autoimmune disease, except vitiligo or resolved childhood asthma/atopy.
- Active infection requiring systemic antibiotic therapy. Known history of human immunodeficiency virus infection. Active Epstein-Barr virus, hepatitis B virus or hepatitis C virus Malignant disease, other than that being treated in this study
Trial locations and contacts
12 sites in 8 countries.
12 sites in 8 countries
United States4 sites
Novartis Investigative Site
Chicago, Illinois, 60637
MD Anderson Cancer Center
Houston, Texas, 77030
The Angeles Clinic and Research Institute
Los Angeles, California, 90025
Seattle Cancer Care Alliance
Seattle, Washington, 98105
Australia2 sites
Novartis Investigative Site
Melbourne, Victoria, 3000
Novartis Investigative Site
North Sydney, New South Wales, 2060
Spain1 site
Novartis Investigative Site
L'Hospitalet de Llobregat, Catalonia, 08907
About this study
Official title: A Phase Ib, Open Label, Multicenter Study of the Safety and Efficacy of MIW815 (ADU-S100) Administered by Intratumoral Injection With PDR001 to Patients With Advanced/Metastatic Solid Tumors or Lymphomas
The purpose of this study was to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics and antitumor activity of MIW815 (ADU-S100) in combination with PDR001.
Read the detailed description
This was a Phase Ib, multi-center, open-label study to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of MIW815(ADU-S100) in combination with the PD-1 checkpoint inhibitor PDR001. Two different schedules were explored in two dose escalation groups in accessible cutaneous or subcutaneous lesions. The optional dose confirmation group exploring intratumoral injection of viscerally located lesions was not opened due to the program's early termination.
Group A included patients with accessible solid tumors and lymphomas. This group received a fixed dose of PDR001 i.v. on day 1 of every 28 day cycle and intratumoral injections of MIW815 (ADU-S100) on days 1, 8 and 15 of every 28 day cycle. Group B included patients with accessible solid tumors and lymphomas. This group received a fixed dose of PDR001 i.v. on day 1 of every 28 day cycle and an intratumoral injection of MIW815 (ADU-S100) on day 1 of every 28 day cycle.
Once the dose and dose schedule had been confirmed, the plan was to open the dose expansion part of the study. However, the expansion phase of the study was not opened to enrollment due to the program's early termination.
- Conditions
- Solid Tumors and Lymphomas
- Being tested
- MIW815, PDR001
- Keywords
- injected lesion, distal lesion, abscopal activity, intratumoral, checkpoint inhibitor, cyclic dinucleotide, programmed cell death
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MIW815Drug
MIW 815 (ADU-S100) is a STING agonist
PDR001Biological
PDR001 is an anti-PD-1 antibody
| Study group | Role | What they receive |
|---|---|---|
| Dosing Schedule A | Experimental | Patients were treated with MIW815 (ADU-S100) via intratumoral injection for 3 weeks followed by one week off in combination with a fixed intravenous dose of PDR001 given once per month Receives: Drug: MIW815; Biological: PDR001 |
| Dosing Schedule B | Experimental | Patients were treated with MIW815 (ADU-S100) via intratumoral injection given once a month in combination with a fixed intravenous dose of PDR001 given once per month Receives: Drug: MIW815; Biological: PDR001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose limiting toxicities (DLTs)
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment with the combination of MIW815 (ADU-S100) and PDR001
Measured: 24 months
Secondary outcomes (16)
AUC inf
The area under the concentration-time curve extrapolated to infinity (mass*time/volume)
Measured: 36 months
AUC last
The area under the concentration (AUC) -time curve calculated to the last quantifiable concentration point (mass* time/volume)
Measured: 36 months
AUC tau
Area under the concentration-time curve calculated to the end of the dosing interval (tau) (mass* time/volume)
Measured: 36 months
Tmax
The time to reach the maximum observed concentration (time)
Measured: 36 months
Cmax
The maximum observed concentration (Cmax) following dose administration (mass/volume)
Measured: 36 months
Lambda_z
Terminal elimination rate constant (1/time)
Measured: 36 months
CL/F
Apparent systemic clearance of drug from the plasma (volume x time -1)
Measured: 36 months
T1/2
Elimination half-life, determined as 0.693/Lambda_z (time)
Measured: 36 months
Vz/F
Apparent volume of distribution during the terminal elimination phase (volume)
Measured: 36 months
Best overall response (BOR)
Best overall response will be summarized
Measured: 36 months
Overall response rate (ORR)
Overall response rate will be summarized with accompanying 90% exact binomial confidence interval (CI).
Measured: 36 months
Progression free survival (PFS)
The survival function will be estimated using the Kaplan-Meier product limit method. Median duration, with a two-sided Brookmeyer-Crowley 90% confidence interval and Kaplan-Meier estimates of survival proportions will be provided at specified time points.
Measured: 36 months
Disease control rate (DCR)
The disease control rate is calculated as the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease
Measured: 36 months
Time to response (TTR)
Time To Response is the time from first dose to first documented response (CR or PR). TTR will be summarized
Measured: 36 months
Duration of Response (DOR)
Duration of response is defined as the time from the date of the first documented response (CR or PR), to the date of first documented progression, or death due to study indication. Estimates will use Kaplan-Meier method
Measured: 36 months
Tumor infiltrating lymphocytes (TIL)
Induction of TILs in the injected lesion (local PD effect) and in a non-injected lesion (distal PD effect) will be assessed using paired tumor samples at screening and on-treatment.
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2017
- Study start8 Sep 2017
- Primary completion18 Dec 2020
- Study completion18 Dec 2020
Why it stopped: Sponsor's decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid Tumors and LymphomasStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- The study was comprised of two treatment arms. Group A included patients with accessible solid tumors and lymphomas. This group received a fixed dose of PDR001 intravenous on day 1 of every 28 day cycle and intratumoral injections of MIW815 (ADU-S100) on days 1, 8 and 15 of every 28 day cycle. Group B included patients with accessible solid tumors and lymphomas. This group received a fixed dose of PDR001 intravenous on day 1 of every 28 day cycle and an intratumoral injection of MIW815 (ADU-S100) on day 1 of every 28 day cycle. Once the maximum tolerated dose and/or recommended dose for expansion had been determined, the plan was to open the expansion part of the study. However, the dose expansion phase of the study was not opened to enrollment due to the program's early termination.
- Masking
- None (open label)
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Nancy Lewis, MD, Study director, Novartis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03172936
- Sponsor's protocol ID
- CMIW815X2102J
- Other IDs
- 2017-000707-25, 2017
- Status last verified
- Apr 2022
- First submitted
- 30 May 2017
- Last updated
- 3 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gogoi H, Mansouri S, Jin L. The Age of Cyclic Dinucleotide Vaccine Adjuvants. Vaccines (Basel). 2020 Aug 13;8(3):453. doi: 10.3390/vaccines8030453.
PubMed 32823563
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib, Open Label, Multicenter Study of the Safety and Efficacy of MIW815 (ADU-S100) Administered by Intratumoral Injection With PDR001 to Patients With Advanced/Metastatic Solid Tumors or Lymphomas
- ClinicalTrials.gov ID
- NCT03172936
- Acronym / sponsor ID
- CMIW815X2102J
- Conditions
- Solid Tumors and Lymphomas
- Keywords
- injected lesion, distal lesion, abscopal activity, intratumoral, checkpoint inhibitor, cyclic dinucleotide, programmed cell death
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor's decision
- Enrolment
- 106 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 8 Sep 2017 (actual)
- Primary completion
- 18 Dec 2020 (actual)
- Study completion
- 18 Dec 2020 (actual)
- First posted
- 1 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics and antitumor activity of MIW815 (ADU-S100) in combination with PDR001.
Detailed description
This was a Phase Ib, multi-center, open-label study to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of MIW815(ADU-S100) in combination with the PD-1 checkpoint inhibitor PDR001. Two different schedules were explored in two dose escalation groups in accessible cutaneous or subcutaneous lesions. The optional dose confirmation group exploring intratumoral injection of viscerally located lesions was not opened due to the program's early termination.
Group A included patients with accessible solid tumors and lymphomas. This group received a fixed dose of PDR001 i.v. on day 1 of every 28 day cycle and intratumoral injections of MIW815 (ADU-S100) on days 1, 8 and 15 of every 28 day cycle. Group B included patients with accessible solid tumors and lymphomas. This group received a fixed dose of PDR001 i.v. on day 1 of every 28 day cycle and an intratumoral injection of MIW815 (ADU-S100) on day 1 of every 28 day cycle.
Once the dose and dose schedule had been confirmed, the plan was to open the dose expansion part of the study. However, the expansion phase of the study was not opened to enrollment due to the program's early termination.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The study was comprised of two treatment arms. Group A included patients with accessible solid tumors and lymphomas. This group received a fixed dose of PDR001 intravenous on day 1 of every 28 day cycle and intratumoral injections of MIW815 (ADU-S100) on days 1, 8 and 15 of every 28 day cycle. Group B included patients with accessible solid tumors and lymphomas. This group received a fixed dose of PDR001 intravenous on day 1 of every 28 day cycle and an intratumoral injection of MIW815 (ADU-S100) on day 1 of every 28 day cycle. Once the maximum tolerated dose and/or recommended dose for expansion had been determined, the plan was to open the expansion part of the study. However, the dose expansion phase of the study was not opened to enrollment due to the program's early termination.
| Arm | Type | Receives |
|---|---|---|
| Dosing Schedule A | Experimental | Drug: MIW815, Biological: PDR001Patients were treated with MIW815 (ADU-S100) via intratumoral injection for 3 weeks followed by one week off in combination with a fixed intravenous dose of PDR001 given once per month |
| Dosing Schedule B | Experimental | Drug: MIW815, Biological: PDR001Patients were treated with MIW815 (ADU-S100) via intratumoral injection given once a month in combination with a fixed intravenous dose of PDR001 given once per month |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- ECOG ≤ 1 Willing to undergo tumor biopsies from injected and distal lesions
Key exclusion criteria (2 listed)
- Symptomatic or untreated leptomeningeal disease. Presence of symptomatic central nervous system metastases Impaired cardiac function or clinically significant cardiac disease Active autoimmune disease or a documented history of autoimmune disease, except vitiligo or resolved childhood asthma/atopy.
- Active infection requiring systemic antibiotic therapy. Known history of human immunodeficiency virus infection. Active Epstein-Barr virus, hepatitis B virus or hepatitis C virus Malignant disease, other than that being treated in this study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MIW815MIW 815 (ADU-S100) is a STING agonist | Drug | Dosing Schedule A, Dosing Schedule B |
| PDR001PDR001 is an anti-PD-1 antibody | Biological | Dosing Schedule A, Dosing Schedule B |
Primary outcome
Incidence of dose limiting toxicities (DLTs)
Time frame: 24 months
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment with the combination of MIW815 (ADU-S100) and PDR001
16 secondary outcomes
AUC inf
Time frame: 36 months
AUC last
Time frame: 36 months
AUC tau
Time frame: 36 months
Tmax
Time frame: 36 months
Cmax
Time frame: 36 months
Lambda_z
Time frame: 36 months
CL/F
Time frame: 36 months
T1/2
Time frame: 36 months
Vz/F
Time frame: 36 months
Best overall response (BOR)
Time frame: 36 months
Overall response rate (ORR)
Time frame: 36 months
Progression free survival (PFS)
Time frame: 36 months
Disease control rate (DCR)
Time frame: 36 months
Time to response (TTR)
Time frame: 36 months
Duration of Response (DOR)
Time frame: 36 months
Tumor infiltrating lymphocytes (TIL)
Time frame: 36 months
Results and safety
The study was stopped early (reason given: Sponsor's decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2022.
- Derived from this study: PubMed 32823563Gogoi H, Mansouri S, Jin L. The Age of Cyclic Dinucleotide Vaccine Adjuvants. Vaccines (Basel). 2020 Aug 13;8(3):453. doi: 10.3390/vaccines8030453.
- Study ResultsLink provided by the sponsor.
- A Plain Language Trial Summary is available on novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nancy Lewis, MD study director
Novartis
12 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MIW815 and PDR001 in people with Solid Tumors and Lymphomas, run by Novartis Pharmaceuticals at 12 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Australia, Canada, Germany, Japan and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Sponsor's decision). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose limiting toxicities (DLTs) (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03172936, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2022.