MelanomaPhase 1/2NCT02404441
Phase I/II Study of PDR001 in Patients With Advanced Malignancies
A Phase 1/2 study testing PDR001 in people with Melanoma and Non-small Sell Lung Cancer (NSCLC), run by Novartis Pharmaceuticals at 41 sites in 14 countries.
Trial summary
The purpose of this "first-in-human" study of PDR001 was to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of PDR001 administered i.v. as a single agent to adult patients with solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma, Non-small Sell Lung Cancer (NSCLC), Triple Negative Breast Cancer
- What is being tested?
- PDR001
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 319 participants
- Where
- 41 sitesin 14 countries
- Study dates
- 27 Apr 2015to 21 Jul 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 have been obtained prior to any screening procedures
- Phase I part: Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease as determined by RECIST version 1.1 (refer to Appendix 1), who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists.
- Phase II part: Patients with advanced/metastatic solid tumors, with at least one measurable lesion as determined by RECIST version 1.1, who have progressed following their last prior therapy, and fit into one of the following groups:
- Group 1a and 1b: NSCLC:
- Patients with NSCLC must have had disease recurrence or progression during or after no more than one prior systemic chemotherapy regimen (platinum doublet-based) for advanced or metastatic disease. Prior maintenance therapy is allowed (e.g. pemetrexed, erlotinib, bevacizumab).
- Only patients with EGFR mutation-negative tumor are eligible (defined as negative for exon 19 deletions and for the L858R mutation in EGFR at a minimum; however, if more extensive EGFR mutation testing has been performed, the tumor must not harbor any known activating EGFR mutations in Exons 18-21 in order to be considered EGFR mutation-negative). All patients must be tested for EGFR mutational status and, for ALK translocation status if no mutation is detected in EGFR. Patients with ALK translocation-positive NSCLC must have had disease progression following treatment with a corresponding inhibitor and no more than one systemic chemotherapy regimen (platinum doublet-based), in any sequence.
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- Group 2: Melanoma:
- All patients must have been tested for BRAF mutations. Patients with V600 mutation positive melanoma must have clinical or radiological evidence of disease progression during or after treatment with a BRAF inhibitor alone or in combination with other agents.
- Group 3: Triple negatice breast cancer.
- Group 4: Anaplastic thyroid cancer
- Patients are not required to have received or progressed on a prior therapy.
- Patients must not be at short term risk for life threatening complications (such as airway compromise or bleeding from locoregional or metastatic disease).
- Chemoradiation and/or surgery should be considered prior to study entry for those patients with locally advanced disease if those therapies are considered to be in the best interest of the patient.
- ECOG Performance Status ≤ 1.
- 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 baseline or at molecular pre-screening if applicable, and during therapy on this study. For patients in the phase II part of the study, exceptions may be granted after documented discussion with Novartis. After a sufficient number of paired biopsies are collected, the decision may be taken to stop the collection of biopsies.
Who cannot join
- History of severe hypersensitivity reactions to other mAbs
- Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition 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.
- Active infection requiring systemic antibiotic therapy.
- HIV infection.
- Active HBV or HCV infection.
- Patients with ocular melanoma.
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- Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment. For cytotoxic agents that have major delayed toxicity, e.g. mitomycin C and nitrosoureas, 4 weeks washout period. For patients receiving anticancer immunotherapies such as CTLA-4 antagonists, 6 weeks is indicated as the washout period.
- Prior PD-1- or PD-L1-directed therapy.
- Patients requiring chronic treatment with systemic steroid therapy, other than replacement-dose steroids in the setting of adrenal insufficiency. Topical, inhaled, nasal and ophthalmic steroids are not prohibited.
- Patients receiving systemic treatment with any immunosuppressive medication (other than steroids as described above).
- Use of any vaccines against infectious diseases (e.g. influenza, varicella, pneumococcus) within 4 weeks of initiation of study treatment.
- Presence of ≥ CTCAE grade 2 toxicity (except alopecia, peripheral neuropathy and ototoxicity, which are excluded if ≥ CTCAE grade 3) due to prior cancer therapy
Trial locations and contacts
41 sites in 14 countries.
41 sites in 14 countries
United States6 sites
The Sidney Kimmel Cancer Center at Johns Hopkins Hospital Johns Hopkins
Baltimore, Maryland, 21287-0013
Massachusetts General Hospital
Boston, Massachusetts, 02114
University of Texas MD Anderson Cancer Center MD Anderson PSC
Houston, Texas, 77030
Sarah Cannon Research Institute SCRI RC
Nashville, Tennessee, 37203
Oregon Health and Science University SC-10
Portland, Oregon, 97239
Huntsman Cancer Institute Univ. of Utah HCI
Salt Lake City, Utah, 84112-0550
Italy5 sites
Novartis Investigative Site
Bologna, BO, 40138
Novartis Investigative Site
Milan, MI, 20132
Novartis Investigative Site
Modena, MO, 41124
Novartis Investigative Site
Naples, 80131
Novartis Investigative Site
Rozzano, MI, 20089
Turkey (Türkiye)5 sites
Novartis Investigative Site
Adana, 01250
Novartis Investigative Site
Edirne, 22030
Novartis Investigative Site
Istanbul, 34303
Novartis Investigative Site
Istanbul, 34890
Novartis Investigative Site
Izmir, 35040
Poland4 sites
Novartis Investigative Site
Gdansk, 80 952
Novartis Investigative Site
Poznan, 60-693
Novartis Investigative Site
Rzeszów, 35-021
Novartis Investigative Site
Warsaw, 02 781
Spain4 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Madrid, 28034
Novartis Investigative Site
Madrid, 28041
Novartis Investigative Site
Madrid, 28050
France3 sites
Novartis Investigative Site
Paris, 75475
Novartis Investigative Site
Toulouse, 31059
Novartis Investigative Site
Villejuif, 94800
Germany3 sites
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Jena, 07740
Novartis Investigative Site
Ulm, 89081
Hungary2 sites
Novartis Investigative Site
Budapest, 1134
Novartis Investigative Site
Debrecen, 4032
Netherlands2 sites
Novartis Investigative Site
Amsterdam, 1066 CX
Novartis Investigative Site
Leiden, 2300 RC
Taiwan2 sites
Novartis Investigative Site
Tainan, Taiwan ROC, 70403
Novartis Investigative Site
Taipei, 10002
Thailand2 sites
Novartis Investigative Site
Bangkok, 10330
Novartis Investigative Site
Songkhla, Hat Yai, 90110
About this study
Official title: Open Label Multicenter Phase I/II Study of the Safety and Efficacy of PDR001 Administered to Patients With Advanced Malignancies
The purpose of this "first-in-human" study of PDR001 was to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of PDR001 administered i.v. as a single agent to adult patients with solid tumors.
By blocking the interaction between PD-1 and its ligands, PD-L1 and PD-L2, PDR001 inhibits the PD-1 immune checkpoint, resulting in activation of an antitumor immune response by activating effector T-cells and inhibiting regulatory T-cells.
Read the detailed description
This study was designed as a phase I/II, multi-center, open-label study starting with a phase I dose escalation part followed by a phase II part.
Although the study had 2 'arms', the phase I part of the study had 5 dosing cohorts and the phase ll part had 5 treatment groups for a total of 10 reporting groups.
PDR001 was administered every 2 weeks until patient experienced unacceptable toxicity, progressive disease per immune related Response Criteria (irRC) and/or treatment was discontinued at the discretion of the investigator or the patient.
- Conditions
- Melanoma, Non-small Sell Lung Cancer (NSCLC), Triple Negative Breast Cancer, Anaplastic Thyroid Cancer, Other Solid Tumors
- Being tested
- PDR001
- Keywords
- Phase I/II, PDR001, Checkpoint inhibitor, PD-1, PD-L1, NSCLC
- Medical subject headings
- Melanoma, Carcinoma, Non-Small-Cell Lung, Triple Negative Breast Neoplasms, Thyroid Carcinoma, Anaplastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PDR001Biological
anti-PD1 antibody
| Study group | Role | What they receive |
|---|---|---|
| patients with solid tumors | Other | Phase I Dose escalation cohorts Receives: Biological: PDR001 |
| Selected tumor types | Other | Phase II expansion: Selected tumor types: melanoma, NSCLC, triple negative breast cancer, anaplastic thyroid cancer Receives: Biological: PDR001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase l: The Exposure (AUC(0-336h)) After First Dose of Treatment at Cycle 3 (Each Cycle = 28 Days)
Estimated the recommended phase 2 dose (RP2D) and/or the maximum tolerated dose (MTD) for PDR001.
AUC0-336h is the AUC from time zero to 336 hour post dose of a measurable concentration sampling time.
Measured: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 3)
Phase l: Incidence of Dose Limiting Toxicities (DLTs)
DLT is defined as an adverse event (AE) or abnormal laboratory value of common terminology criteria for adverse events (CTCAE) grade ≥ 3 assessed as unrelated to disease, disease progression, inter-current illness or concomitant medications, which occurs within the first cycle of treatment with PDR001 during the dose escalation part of the study for which relationship to study treatment cannot be ruled out, with some exceptions.
Measured: 8 months
Phase ll: Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
ORR is the percentage of participants with a best overall response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 CR = at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required.
PR = at least 2 determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required.
RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.
Measured: 61 months
Secondary outcomes (23)
Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau)
AUC0-336h is the AUC from time zero to 336 hour post dose of a measurable concentration sampling time.
AUClast: The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1).
AUCinf: The AUC from time zero to infinity (mass x time x volume-1). AUCtau: The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1).
Measured: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 1 & 3)
Phase I: Serum Pharmacokinetic (PK) Parameter Cmax
The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1)
Measured: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (Cycle 1 & 3)
Phase I: Serum Pharmacokinetic (PK) Parameter Tmax
The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time)
Measured: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 1 & 3)
Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau)
AUC0-336h is the AUC from time zero to 336 hour post dose of a measurable concentration sampling time.
AUClast: The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1).
AUCinf: The AUC from time zero to infinity (mass x time x volume-1). AUCtau: The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1).
Measured: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 1 & 3)
Phase ll: Serum Pharmacokinetic (PK) Parameter Cmax
The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1)
Measured: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (Cycle 1 & 3)
Phase ll: Serum Pharmacokinetic (PK) Parameter Tmax
The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time)
Measured: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (Cycle 1 & 3)
Phase I: Presence and/or Concentration of Anti-PDR001
Assessed PDR001 anti-drug anti-body (ADA) incidence in Phase I patients - the emergence of anti-PDR001 antibodies following one or more intravenous (i.v.) infusions of PDR001. Each cycle = 28 days; End of treatment was expected to be on average 1 year after the start of study treatment.
Measured: 42 months
Phase II: Presence and/or Concentration of Anti-PDR001
Assessed PDR001 anti-drug anti-body (ADA) incidence in Phase I patients - the emergence of anti-PDR001 antibodies following one or more intravenous (i.v.) infusions of PDR001. Each cycle = 28 days; End of treatment was expected to be on average 1 year after the start of study treatment.
For Treatment -induced ADA-positive, Percentage was based on subjects ADA-negative at baseline.
For Treatment-boosted ADA-positive, Percentage was based on subjects ADA-positive at baseline.
Measured: 42 months
Phase l: Overall Response Rate (ORR) as Per Investigator Based on RECIST v1.1
ORR is the percentage of participants with a best overall response of complete response CR or partial response PR as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required.
PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required.
RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.
Measured: 27 months
Phase l: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1
DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD).
CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required.
SD = at least one SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR).
RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.
Measured: 27 months
Phase l: Progression Free Survival (PFS) as Per RECIST v1.1
PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates.
RECIST criteria, published in February 2000 by an international collaboration including the European Organization for Research and Treatment of Cancer (EORTC), National Cancer Institute of the United States, and the National Cancer Institute of Canada Clinical Trials Group, is a Response evaluation criteria in solid tumors is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.
RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.
Measured: 27 months
Phase I: Duration of Response (DOR) as Per RECIST v1.1
DOR is measured from the time measurement criteria are met for CR or PR (whichever status is recorded first) until the first date that recurrence or PD is objectively documented. CR = at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required; PR = at least 2 determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required; PD =progression <= 12 weeks after randomization/start of treatment (and not qualifying for CR, PR or SD). SD = at least 1 SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment
Measured: 27 months
Phase l Only: Overall Response Rate (ORR) as Per Investigator Based on Immune Related Response Criteria (irRC)
ORR is the percentage of participants with a best overall response of complete response (CR) or partial response (PR) as per irRC.
CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required.
PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required.
The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug.
Measured: 27 months
Phase l Only: Disease Control Rate (DCR) as Per Investigator Based on irRC
DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD).
CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required.
SD = at least one SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR).
The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug.
Measured: 27 months
Phase l Only: Progression Free Survival (PFS) as Per irRC
PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates.
The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug.
Measured: 27 months
Phase I: Duration of Response (DOR) as Per irRC
DOR: measured from time measurement criteria are met for CR or PR (whichever status is recorded first) until first date that recurrence or PD is objectively documented CR: at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required PR: at least 1 determination of PR or better at least 4 weeks apart before progression (\& not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required PD: progression <= start of treatment (\& not qualifying for CR, PR or SD) SD: at least 1 SD assessment (or better) > 6 weeks after randomization/start of treatment (\& not qualifying for CR or PR) irRC is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug
Measured: 61 Days
Phase II: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1
DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD).
CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required.
SD = at least one SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR).
RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.
Measured: 61 months
Phase II: Progression Free Survival as Per Investigator Based on RECIST v1.1
PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates.
RECIST criteria, published in February 2000 by an international collaboration including the European Organization for Research and Treatment of Cancer (EORTC), National Cancer Institute of the United States, and the National Cancer Institute of Canada Clinical Trials Group, is a Response evaluation criteria in solid tumors is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.
Measured: 61 months
Phase II: Duration of Response (DOR) as Per Investigator Based on RECIST v1.1
DOR is measured from the time measurement criteria are met for CR or PR (whichever status is recorded first) until the first date that recurrence or PD is objectively documented.
CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required.
PD = progression <= start of treatment (and not qualifying for CR, PR or SD). SD = at least one SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR).
RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.
Measured: 61 months
Phase II: Overall Response Rate (ORR) as Per Investigator Based on irRC
ORR is the percentage of participants with a best overall response CR or PR as per irRC.
CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required.
PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required.
The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug.
Measured: 61 months
Phase II: Disease Control Rate (DCR) as Per Investigator Based on irRC
DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD).
CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required.
SD = at least one SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR).
The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug.
Measured: 61 months
Phase II: Progression Free Survival (PFS) Per irRC
PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates.
The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug.
Measured: 61 months
Phase II: Duration of Response (DOR) Per irRC
DOR: measured from time measurement criteria are met for CR or PR (whichever status is recorded first) until first date that recurrence or PD is objectively documented CR: at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required PR: at least 1 determination of PR or better at least 4 weeks apart before progression (\& not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required PD: progression <= start of treatment (\& not qualifying for CR, PR or SD) SD: at least 1 SD assessment (or better) > 6 weeks after randomization/start of treatment (\& not qualifying for CR or PR) irRC is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug
Measured: 61 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2015 (estimated)
- Study start27 Apr 2015
- Primary completion21 Jul 2020
- Study completion21 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- Although the study had 2 'arms', the phase I part of the study had 5 dosing cohorts and the phase ll part had 5 treatment groups for a total of 10 reporting groups.
- Masking
- None (open label)
- Enrolment
- 319 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
- NCT02404441
- Sponsor's protocol ID
- CPDR001X2101
- Other IDs
- 2014-003929-17, 2014
- Status last verified
- Aug 2022
- First submitted
- 20 Mar 2015
- Last updated
- 3 Aug 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Publications
Capdevila J, Wirth LJ, Ernst T, Ponce Aix S, Lin CC, Ramlau R, Butler MO, Delord JP, Gelderblom H, Ascierto PA, Fasolo A, Fuhrer D, Hutter-Kronke ML, Forde PM, Wrona A, Santoro A, Sadow PM, Szpakowski S, Wu H, Bostel G, Faris J, Cameron S, Varga A, Taylor M. PD-1 Blockade in Anaplastic Thyroid Carcinoma. J Clin Oncol. 2020 Aug 10;38(23):2620-2627. doi: 10.1200/JCO.19.02727. Epub 2020 May 4.
PubMed 32364844Naing A, Gainor JF, Gelderblom H, Forde PM, Butler MO, Lin CC, Sharma S, Ochoa de Olza M, Varga A, Taylor M, Schellens JHM, Wu H, Sun H, Silva AP, Faris J, Mataraza J, Cameron S, Bauer TM. A first-in-human phase 1 dose escalation study of spartalizumab (PDR001), an anti-PD-1 antibody, in patients with advanced solid tumors. J Immunother Cancer. 2020 Mar;8(1):e000530. doi: 10.1136/jitc-2020-000530.
PubMed 32179633
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label Multicenter Phase I/II Study of the Safety and Efficacy of PDR001 Administered to Patients With Advanced Malignancies
- ClinicalTrials.gov ID
- NCT02404441
- Acronym / sponsor ID
- CPDR001X2101
- Conditions
- Melanoma, Non-small Sell Lung Cancer (NSCLC), Triple Negative Breast Cancer, Anaplastic Thyroid Cancer, Other Solid Tumors
- Keywords
- Phase I/II, PDR001, Checkpoint inhibitor, PD-1, PD-L1, NSCLC
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 319 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 27 Apr 2015 (actual)
- Primary completion
- 21 Jul 2020 (actual)
- Study completion
- 21 Jul 2020 (actual)
- First posted
- 31 Mar 2015 (estimated)
- Results
- Posted 29 Sep 2021
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 "first-in-human" study of PDR001 was to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of PDR001 administered i.v. as a single agent to adult patients with solid tumors.
By blocking the interaction between PD-1 and its ligands, PD-L1 and PD-L2, PDR001 inhibits the PD-1 immune checkpoint, resulting in activation of an antitumor immune response by activating effector T-cells and inhibiting regulatory T-cells.
Detailed description
This study was designed as a phase I/II, multi-center, open-label study starting with a phase I dose escalation part followed by a phase II part.
Although the study had 2 'arms', the phase I part of the study had 5 dosing cohorts and the phase ll part had 5 treatment groups for a total of 10 reporting groups.
PDR001 was administered every 2 weeks until patient experienced unacceptable toxicity, progressive disease per immune related Response Criteria (irRC) and/or treatment was discontinued at the discretion of the investigator or the patient.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Although the study had 2 'arms', the phase I part of the study had 5 dosing cohorts and the phase ll part had 5 treatment groups for a total of 10 reporting groups.
| Arm | Type | Receives |
|---|---|---|
| patients with solid tumors | Other | Biological: PDR001Phase I Dose escalation cohorts |
| Selected tumor types | Other | Biological: PDR001Phase II expansion: Selected tumor types: melanoma, NSCLC, triple negative breast cancer, anaplastic thyroid cancer |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Written informed consent must have been obtained prior to any screening procedures
- Phase I part: Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease as determined by RECIST version 1.1 (refer to Appendix 1), who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists.
- Phase II part: Patients with advanced/metastatic solid tumors, with at least one measurable lesion as determined by RECIST version 1.1, who have progressed following their last prior therapy, and fit into one of the following groups:
- Patients with NSCLC must have had disease recurrence or progression during or after no more than one prior systemic chemotherapy regimen (platinum doublet-based) for advanced or metastatic disease. Prior maintenance therapy is allowed (e.g. pemetrexed, erlotinib, bevacizumab).
- Only patients with EGFR mutation-negative tumor are eligible (defined as negative for exon 19 deletions and for the L858R mutation in EGFR at a minimum; however, if more extensive EGFR mutation testing has been performed, the tumor must not harbor any known activating EGFR mutations in Exons 18-21 in order to be considered EGFR mutation-negative). All patients must be tested for EGFR mutational status and, for ALK translocation status if no mutation is detected in EGFR. Patients with ALK translocation-positive NSCLC must have had disease progression following treatment with a corresponding inhibitor and no more than one systemic chemotherapy regimen (platinum doublet-based), in any sequence.
Key exclusion criteria (12 listed)
- History of severe hypersensitivity reactions to other mAbs
- Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition 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.
- Active infection requiring systemic antibiotic therapy.
- HIV infection.
- Active HBV or HCV infection.
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 |
|---|---|---|
| PDR001anti-PD1 antibody | Biological | Selected tumor types, patients with solid tumors |
Primary outcome
Phase l: The Exposure (AUC(0-336h)) After First Dose of Treatment at Cycle 3 (Each Cycle = 28 Days)
Time frame: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 3)
Estimated the recommended phase 2 dose (RP2D) and/or the maximum tolerated dose (MTD) for PDR001. AUC0-336h is the AUC from time zero to 336 hour post dose of a measurable concentration sampling time.
Phase l: Incidence of Dose Limiting Toxicities (DLTs)
Time frame: 8 months
DLT is defined as an adverse event (AE) or abnormal laboratory value of common terminology criteria for adverse events (CTCAE) grade ≥ 3 assessed as unrelated to disease, disease progression, inter-current illness or concomitant medications, which occurs within the first cycle of treatment with PDR001 during the dose escalation part of the study for which relationship to study treatment cannot be ruled out, with some exceptions.
Phase ll: Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
Time frame: 61 months
ORR is the percentage of participants with a best overall response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 CR = at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required. PR = at least 2 determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required. RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.
23 secondary outcomes
Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau)
Time frame: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 1 & 3)
Phase I: Serum Pharmacokinetic (PK) Parameter Cmax
Time frame: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (Cycle 1 & 3)
Phase I: Serum Pharmacokinetic (PK) Parameter Tmax
Time frame: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 1 & 3)
Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau)
Time frame: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 1 & 3)
Phase ll: Serum Pharmacokinetic (PK) Parameter Cmax
Time frame: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (Cycle 1 & 3)
Phase ll: Serum Pharmacokinetic (PK) Parameter Tmax
Time frame: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (Cycle 1 & 3)
Phase I: Presence and/or Concentration of Anti-PDR001
Time frame: 42 months
Phase II: Presence and/or Concentration of Anti-PDR001
Time frame: 42 months
Phase l: Overall Response Rate (ORR) as Per Investigator Based on RECIST v1.1
Time frame: 27 months
Phase l: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1
Time frame: 27 months
Phase l: Progression Free Survival (PFS) as Per RECIST v1.1
Time frame: 27 months
Phase I: Duration of Response (DOR) as Per RECIST v1.1
Time frame: 27 months
Phase l Only: Overall Response Rate (ORR) as Per Investigator Based on Immune Related Response Criteria (irRC)
Time frame: 27 months
Phase l Only: Disease Control Rate (DCR) as Per Investigator Based on irRC
Time frame: 27 months
Phase l Only: Progression Free Survival (PFS) as Per irRC
Time frame: 27 months
Phase I: Duration of Response (DOR) as Per irRC
Time frame: 61 Days
Phase II: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1
Time frame: 61 months
Phase II: Progression Free Survival as Per Investigator Based on RECIST v1.1
Time frame: 61 months
Phase II: Duration of Response (DOR) as Per Investigator Based on RECIST v1.1
Time frame: 61 months
Phase II: Overall Response Rate (ORR) as Per Investigator Based on irRC
Time frame: 61 months
Phase II: Disease Control Rate (DCR) as Per Investigator Based on irRC
Time frame: 61 months
Phase II: Progression Free Survival (PFS) Per irRC
Time frame: 61 months
Phase II: Duration of Response (DOR) Per irRC
Time frame: 61 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32364844Capdevila J, Wirth LJ, Ernst T, Ponce Aix S, Lin CC, Ramlau R, Butler MO, Delord JP, Gelderblom H, Ascierto PA, Fasolo A, Fuhrer D, Hutter-Kronke ML, Forde PM, Wrona A, Santoro A, Sadow PM, Szpakowski S, Wu H, Bostel G, Faris J, Cameron S, Varga A, Taylor M. PD-1 Blockade in Anaplastic Thyroid Carcinoma. J Clin Oncol. 2020 Aug 10;38(23):2620-2627. doi: 10.1200/JCO.19.02727. Epub 2020 May 4.
- Derived from this study: PubMed 32179633Naing A, Gainor JF, Gelderblom H, Forde PM, Butler MO, Lin CC, Sharma S, Ochoa de Olza M, Varga A, Taylor M, Schellens JHM, Wu H, Sun H, Silva AP, Faris J, Mataraza J, Cameron S, Bauer TM. A first-in-human phase 1 dose escalation study of spartalizumab (PDR001), an anti-PD-1 antibody, in patients with advanced solid tumors. J Immunother Cancer. 2020 Mar;8(1):e000530. doi: 10.1136/jitc-2020-000530.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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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
41 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PDR001 in people with Melanoma and Non-small Sell Lung Cancer (NSCLC), run by Novartis Pharmaceuticals at 41 sites in 14 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 15 inclusion and 12 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 3 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 41 sites in United States, Italy, Turkey (Türkiye), Poland, Spain and 9 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Phase l: The Exposure (AUC(0-336h)) After First Dose of Treatment at Cycle 3 (Each Cycle = 28 Days) (time frame: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 3)). The study lists 3 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 NCT02404441, 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 3 Aug 2022.