Breast CancerPhase 1NCT02947165
Phase I/Ib Study of NIS793 in Combination With PDR001 in Patients With Advanced Malignancies.
A Phase 1 study testing NIS793 and PDR001 in people with Breast Cancer and Lung Cancer, run by Novartis Pharmaceuticals at 12 sites in 9 countries.
Trial summary
To characterize the safety and tolerability of NIS793 as single agent and in combination with PDR001 and to identify recommended doses for future studies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Lung Cancer, Hepatocellular Cancer
- What is being tested?
- NIS793 and PDR001
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 12 sitesin 9 countries
- Study dates
- 25 Apr 2017to 18 Jun 2021
- 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
- Written informed consent must be obtained prior to any screening procedures.
- Patient (male or female) ≥ 18 years of age.
- Escalation: Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease as determined by RECIST version 1.1 who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists.
- Expansion: Patients with advanced/metastatic solid tumors, with at least one measurable lesion as determined by RECIST version 1.1, who have progressed despite standard therapy following their last prior therapy or are intolerant to standard therapy and fit into one of the following groups: Group 1: NSCLC resistant to anti-PD-1/PD-L1; Group 2: TNBC; Group 3: HCC; Group 4: MSS-CRC; Group 5: pancreatic; Group 6 ccRCC resistant to anti-PD-1/PD-L1.
- Resistance to anti-PD-1/PD-L1 therapy is defined as: Documented progressive disease occurring while on/or within 6 months after anti-PD-1 and/or anti-PD-L1 agent (single or combination) received as the last therapy prior to enrollment.
- ECOG Performance Status ≤ 2.
- Patients must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy. Patient must be willing to undergo a new tumor biopsy at screening, and during therapy on this study. Exceptions may be made on a case by case basis after documented discussion with Novartis.
Who cannot join
- History of severe hypersensitivity reactions to study treatment ingredients or other monoclonal antibodies and components of study drug.
- Patients with active, known or suspected autoimmune disease. Note: Patients with vitiligo, type I diabetes mellitus, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- HIV infection.
- Active HBV or HCV infection.
- Other protocol-defined inclusion/exclusion criteria may apply.
Trial locations and contacts
12 sites in 9 countries.
12 sites in 9 countries
United States2 sites
Sarah Cannon Research Institute SC
Nashville, Tennessee, 37203
Huntsman Cancer Institute SC
Salt Lake City, Utah, 84112
Germany2 sites
Novartis Investigative Site
Ulm, 89081
Novartis Investigative Site
Würzburg, 97080
Italy2 sites
Novartis Investigative Site
Milan, MI, 20132
Novartis Investigative Site
Rozzano, MI, 20089
About this study
Official title: A Phase I/Ib, Open-label, Multi-center Dose Escalation Study of NIS793 in Combination With PDR001 in Adult Patients With Advanced Malignancies
To characterize the safety and tolerability of NIS793 as single agent and in combination with PDR001 and to identify recommended doses for future studies.
- Conditions
- Breast Cancer, Lung Cancer, Hepatocellular Cancer, Colorectal Cancer, Pancreatic Cancer, Renal Cancer
- Being tested
- NIS793, PDR001
- Medical subject headings
- Breast Neoplasms, Lung Neoplasms, Liver Neoplasms, Colorectal Neoplasms, Pancreatic Neoplasms, Kidney Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NIS793Drug
Anti-TGF beta antibody tested on a Q3W regimen or alternative Q2W regimen.
PDR001Drug
Anti-PD-1 antibody tested on a Q3W regimen or alternative Q4W regimen.
| Study group | Role | What they receive |
|---|---|---|
| NIS793 | Experimental | Not described Receives: Drug: NIS793 |
| NIS793 + PDR001 | Experimental | Not described Receives: Drug: NIS793; Drug: PDR001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of DLTs, AEs, SAEs and dose reductions / interruptions for NIS793
Measured: Up to 90 days after end of treatment
Incidence of DLTs, AEs, SAEs and dose reductions/interruptions for NIS793 in combination with PDR001
Measured: Up to 150 days after end of treatment
Secondary outcomes (14)
Best overall response (BOR)
Evaluate the anti-tumor activity per RECIST as well as per immune related Response Criteria (irRC) of NIS793 as single agent and in combination with PDR001 every 2 cycles from start of treatment until cycle 9 then every 3 cycles until end of treatment (if applicable).
Measured: 48 months
Disease control rate (DCR)
Evaluate the anti-tumor activity per RECIST as well as per immune related Response Criteria (irRC) of NIS793 as single agent and in combination with PDR001every 2 cycles from start of treatment until cycle 9 then every 3 cycles until end of treatment (if applicable).
Measured: 48 months
Overall response rate (ORR)
Evaluate the anti-tumor activity per RECIST as well as per immune related Response Criteria (irRC) of NIS793 as single agent and in combination with PDR001 every2 cycles from start of treatment until cycle 9 then every 3 cycles until end of treatment (if applicable).
Measured: 48 months
Progression free survival (PFS)
Evaluate the anti-tumor activity per RECIST as well as per immune related Response Criteria (irRC) of NIS793 as single agent and in combination with PDR001 every 2 cycles from start of treatment until cycle 9 then every 3 cycles until end of treatment. During disease progression f/u, every 8 weeks for 40 weeks, then every 12 weeks.
Measured: 48 months
Duration of response (DOR)
Evaluate the anti-tumor activity per RECIST as well as per immune related Response Criteria (irRC) of NIS793 as single agent and in combination with PDR001 every 2 cycles from start of treatment until cycle 9 then every 3 cycles until end of treatment (if applicable).
Measured: 48 months
Serum concentration-time profiles of NIS793 single agent and NIS793 in combination with PDR001
Evaluate serum concentration of NIS793 and PDR001 up to 8 cycles after start of treatment and at end of treatment.
Measured: 48 months
Presence of anti-NIS793 and anti-PDR001 antibodies
Assess the emergence of anti-NIS793 and anti-PDR001 antibodies up to 8 cycles after start of treatment and at end of treatment.
Measured: 48 months
Concentration of anti-NIS793 and anti-PDR001 antibodies
Assess the concentration of anti-NIS793 and anti-PDR001 antibodies up to 8 cycles after start of treatment and at end of treatment.
Measured: 48 months
Area under the curve (AUC) for NIS793 single agent and NIS793 in combination with PDR001.
Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.
Measured: 48 months
Cmax for NIS793 single agent and NIS793 in combination with PDR001.
Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.
Measured: 48 months
Tmax for NIS793 single agent and NIS793 in combination with PDR001.
Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.
Measured: 48 months
Half life of NIS793 as single agent and in combination with PDR001.
Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.
Measured: 48 months
Characterization of tumor infiltrating lymphocytes (TILs) by H&E
Assess change from baseline of immune infiltrates in tumor biopsies after 2 cycles of treatment.
Measured: 48 months
Characterization of tumor infiltrating lymphocytes by immunohistochemistry using markers such as CD8 and PD-L1
Assess change from baseline in immunological markers in tumor biopsies after 2 cycles of treatment.
Measured: 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2016 (estimated)
- Study start25 Apr 2017
- Primary completion18 Jun 2021
- Study completion18 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies 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
- Masking
- None (open label)
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02947165
- Sponsor's protocol ID
- CNIS793X2101
- Other IDs
- 2016-003044-36, 2016
- Status last verified
- Jan 2022
- First submitted
- 18 Oct 2016
- Last updated
- 31 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bauer TM, Santoro A, Lin CC, Garrido-Laguna I, Joerger M, Greil R, Spreafico A, Yau T, Goebeler ME, Hutter-Kronke ML, Perotti A, Juif PE, Lu D, Barys L, Cremasco V, Pelletier M, Evans H, Fabre C, Doi T. Phase I/Ib, open-label, multicenter, dose-escalation study of the anti-TGF-beta monoclonal antibody, NIS793, in combination with spartalizumab in adult patients with advanced tumors. J Immunother Cancer. 2023 Nov 29;11(11):e007353. doi: 10.1136/jitc-2023-007353.
PubMed 38030303Dodagatta-Marri E, Meyer DS, Reeves MQ, Paniagua R, To MD, Binnewies M, Broz ML, Mori H, Wu D, Adoumie M, Del Rosario R, Li O, Buchmann T, Liang B, Malato J, Arce Vargus F, Sheppard D, Hann BC, Mirza A, Quezada SA, Rosenblum MD, Krummel MF, Balmain A, Akhurst RJ. alpha-PD-1 therapy elevates Treg/Th balance and increases tumor cell pSmad3 that are both targeted by alpha-TGFbeta antibody to promote durable rejection and immunity in squamous cell carcinomas. J Immunother Cancer. 2019 Mar 4;7(1):62. doi: 10.1186/s40425-018-0493-9.
PubMed 30832732
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/Ib, Open-label, Multi-center Dose Escalation Study of NIS793 in Combination With PDR001 in Adult Patients With Advanced Malignancies
- ClinicalTrials.gov ID
- NCT02947165
- Acronym / sponsor ID
- CNIS793X2101
- Conditions
- Breast Cancer, Lung Cancer, Hepatocellular Cancer, Colorectal Cancer, Pancreatic Cancer, Renal Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 25 Apr 2017 (actual)
- Primary completion
- 18 Jun 2021 (actual)
- Study completion
- 18 Jun 2021 (actual)
- First posted
- 27 Oct 2016 (estimated)
- 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.
To characterize the safety and tolerability of NIS793 as single agent and in combination with PDR001 and to identify recommended doses for future studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NIS793 | Experimental | Drug: NIS793 |
| NIS793 + PDR001 | Experimental | Drug: NIS793, Drug: PDR001 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Written informed consent must be obtained prior to any screening procedures.
- Patient (male or female) ≥ 18 years of age.
- Escalation: Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease as determined by RECIST version 1.1 who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists.
- Expansion: Patients with advanced/metastatic solid tumors, with at least one measurable lesion as determined by RECIST version 1.1, who have progressed despite standard therapy following their last prior therapy or are intolerant to standard therapy and fit into one of the following groups: Group 1: NSCLC resistant to anti-PD-1/PD-L1; Group 2: TNBC; Group 3: HCC; Group 4: MSS-CRC; Group 5: pancreatic; Group 6 ccRCC resistant to anti-PD-1/PD-L1.
- Resistance to anti-PD-1/PD-L1 therapy is defined as: Documented progressive disease occurring while on/or within 6 months after anti-PD-1 and/or anti-PD-L1 agent (single or combination) received as the last therapy prior to enrollment.
Key exclusion criteria (5 listed)
- History of severe hypersensitivity reactions to study treatment ingredients or other monoclonal antibodies and components of study drug.
- Patients with active, known or suspected autoimmune disease. Note: Patients with vitiligo, type I diabetes mellitus, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- HIV infection.
- Active HBV or HCV infection.
- Other protocol-defined inclusion/exclusion criteria may apply.
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 |
|---|---|---|
| NIS793Anti-TGF beta antibody tested on a Q3W regimen or alternative Q2W regimen. | Drug | NIS793, NIS793 + PDR001 |
| PDR001Anti-PD-1 antibody tested on a Q3W regimen or alternative Q4W regimen. | Drug | NIS793 + PDR001 |
Primary outcome
Incidence of DLTs, AEs, SAEs and dose reductions / interruptions for NIS793
Time frame: Up to 90 days after end of treatment
Incidence of DLTs, AEs, SAEs and dose reductions/interruptions for NIS793 in combination with PDR001
Time frame: Up to 150 days after end of treatment
14 secondary outcomes
Best overall response (BOR)
Time frame: 48 months
Disease control rate (DCR)
Time frame: 48 months
Overall response rate (ORR)
Time frame: 48 months
Progression free survival (PFS)
Time frame: 48 months
Duration of response (DOR)
Time frame: 48 months
Serum concentration-time profiles of NIS793 single agent and NIS793 in combination with PDR001
Time frame: 48 months
Presence of anti-NIS793 and anti-PDR001 antibodies
Time frame: 48 months
Concentration of anti-NIS793 and anti-PDR001 antibodies
Time frame: 48 months
Area under the curve (AUC) for NIS793 single agent and NIS793 in combination with PDR001.
Time frame: 48 months
Cmax for NIS793 single agent and NIS793 in combination with PDR001.
Time frame: 48 months
Tmax for NIS793 single agent and NIS793 in combination with PDR001.
Time frame: 48 months
Half life of NIS793 as single agent and in combination with PDR001.
Time frame: 48 months
Characterization of tumor infiltrating lymphocytes (TILs) by H&E
Time frame: 48 months
Characterization of tumor infiltrating lymphocytes by immunohistochemistry using markers such as CD8 and PD-L1
Time frame: 48 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2022.
- Derived from this study: PubMed 38030303Bauer TM, Santoro A, Lin CC, Garrido-Laguna I, Joerger M, Greil R, Spreafico A, Yau T, Goebeler ME, Hutter-Kronke ML, Perotti A, Juif PE, Lu D, Barys L, Cremasco V, Pelletier M, Evans H, Fabre C, Doi T. Phase I/Ib, open-label, multicenter, dose-escalation study of the anti-TGF-beta monoclonal antibody, NIS793, in combination with spartalizumab in adult patients with advanced tumors. J Immunother Cancer. 2023 Nov 29;11(11):e007353. doi: 10.1136/jitc-2023-007353.
- Derived from this study: PubMed 30832732Dodagatta-Marri E, Meyer DS, Reeves MQ, Paniagua R, To MD, Binnewies M, Broz ML, Mori H, Wu D, Adoumie M, Del Rosario R, Li O, Buchmann T, Liang B, Malato J, Arce Vargus F, Sheppard D, Hann BC, Mirza A, Quezada SA, Rosenblum MD, Krummel MF, Balmain A, Akhurst RJ. alpha-PD-1 therapy elevates Treg/Th balance and increases tumor cell pSmad3 that are both targeted by alpha-TGFbeta antibody to promote durable rejection and immunity in squamous cell carcinomas. J Immunother Cancer. 2019 Mar 4;7(1):62. doi: 10.1186/s40425-018-0493-9.
- 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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
12 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NIS793 and PDR001 in people with Breast Cancer and Lung Cancer, run by Novartis Pharmaceuticals at 12 sites in 9 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 7 inclusion and 5 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: finished, as of the sponsor's last update on 31 Jan 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, Germany, Italy, Austria, Canada and 4 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 DLTs, AEs, SAEs and dose reductions / interruptions for NIS793 (time frame: Up to 90 days after end of treatment). The study lists 2 primary outcomes in all. 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 NCT02947165, which also lists 2 linked publications.
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 31 Jan 2022.