Pancreatic CancerPhase 1NCT01351103
A Study of LGK974 in Patients With Malignancies Dependent on Wnt Ligands
A Phase 1 study testing LGK974 and PDR001 in people with Pancreatic Cancer and BRAF Mutant Colorectal Cancer, run by Novartis Pharmaceuticals at 20 sites in 7 countries.
Trial summary
The primary purpose of this study was to find the recommended dose of LGK974 as a single agent and in combination with PDR001 that can be safely given to adult patients with selected solid malignancies that had progressed despite standard therapy or for which no effective standard therapy existed. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Cancer, BRAF Mutant Colorectal Cancer, Melanoma
- What is being tested?
- LGK974 and PDR001
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 185 participants
- Where
- 20 sitesin 7 countries
- Study dates
- 1 Dec 2011to 17 Jun 2024
- 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
- Diagnosis of locally advanced or metastatic cancer that has progressed despite standard therapy or for which no effective standard therapy exists and histological confirmation of one of the following diseases indicated below:
- Single Agent Dose escalation part:documented B-RAF mutant colorectal cancer or pancreatic adenocarcinoma. In addition, tumors of any histological origin with documented genetic alterations upstream in the Wnt signaling pathway are eligible with prior agreement with Novartis.
- Single Agent Dose expansion part: documented B-RAF mutant colorectal cancer with documented RNF43 mutation and/or RSPO fusion or pancreatic adenocarcinoma with documented RNF43 mutation. In addition, patients with tumors of any histological origin with documented genetic alterations upstream in the Wnt signaling pathway (e.g. RNF43 or RSPO fusion) are eligible with prior agreement with Novartis
- LGK974 with PDR001: Dose escalation: patients with the following cancers that were previously treated with anti-PD-1 therapy and whose best response on that therapy was progressive disease (i.e. primary refractory): melanoma, lung SCC, HNSCC. Patients with esophageal SCC, cervical SCC or TNBC who are either naïve or primary refractory to prior anti-PD-1 therapy.
- LGK974 with PDR001: Dose expansion: patients with:
- cutaneous melanoma that was primary refractory to prior anti-PD-1 therapy, defined as a best response of progressive disease or stable disease for <= 4 months, or disease recurrence with the first 6 months of adjuvant therapy. Patients with BRAF V600-mutant melanoma must have also received and been failed by prior systemic therapy with BRAF V600 inhibitor, with or without a MEK inhibitor.
- Cutaneous melanoma with acquired resistance to prior anti-PD-1 therapy, defined as progressive disease following response (PR or CR) or following stable disease for > 4 months. Patients with BRAF V600-mutant melanoma must have also received and been failed by prior systemic therapy with a BRAF V600 inhibitor, with or without a MEK inhibitor.
Who cannot join
- Impaired cardiac function
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of LGK974 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
- Brain metastases that have not been adequately treated
- Malignant disease other than that being treated in this study
- Laboratory abnormalities as specified in the protocol
- Osteoporosis, osteopenia
Show all 10Show fewer
- Bone fractures within the past year
- Pathologic bone fracture
- Active, known or suspected autoimmune disease or severe hypersensitivity reactions to other monoclonal antibodies
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
20 sites in 7 countries.
20 sites in 7 countries
Spain7 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Barcelona, Catalonia, 08036
Novartis Investigative Site
L'Hospitalet de Llobregat, Catalonia, 08907
Novartis Investigative Site
Madrid, 28009
Novartis Investigative Site
Madrid, 28040
Novartis Investigative Site
Madrid, 28050
Novartis Investigative Site
Valencia, Valencia, 46010
United States6 sites
University of Michigan Comprehensive Cancer Center Onc Dept.
Ann Arbor, Michigan, 48109-0944
Sidney Kimmel Comprehensive Cancer Center Johns Hopkins
Baltimore, Maryland, 21287-0013
Dana Farber Cancer Institute SC-7
Boston, Massachusetts, 02215
Karmanos Cancer Institute Wayne St
Detroit, Michigan, 48201
University of Texas/MD Anderson Cancer Center MD Anderson 2
Houston, Texas, 77030-4009
UCLA School of Medicine
Los Angeles, California, 90024
Italy2 sites
Novartis Investigative Site
Milan, MI, 20133
Novartis Investigative Site
Naples, 80131
Netherlands2 sites
Novartis Investigative Site
Rotterdam, South Holland, 3015 GD
Novartis Investigative Site
Utrecht, 3584CX
About this study
Official title: A Phase I, Open-label, Dose Escalation Study of Oral LGK974 in Patients With Malignancies Dependent on Wnt Ligands
The primary purpose of this study was to find the recommended dose of LGK974 as a single agent and in combination with PDR001 that can be safely given to adult patients with selected solid malignancies that had progressed despite standard therapy or for which no effective standard therapy existed.
Read the detailed description
This open-label multicenter phase 1 dose escalation study was the first to administer LGK974 as a single agent or in combination with PDR001 in humans.
The study comprised of 2 parts: a dose escalation of LGK974 as a single agent, followed by a safety expansion in specific disease indications; and a dose escalation of LGK974 in combination with PDR001, followed by a safety expansion in cutaneous melanoma.
- Conditions
- Pancreatic Cancer, BRAF Mutant Colorectal Cancer, Melanoma, Triple Negative Breast Cancer, Head and Neck Squamous Cell Cancer, Cervical Squamous Cell Cancer
- Being tested
- LGK974, PDR001
- Keywords
- LGK974, pancreatic adenocarcinoma, BRAF mutant colorectal cancer, RNF43 mutation, RSPO fusion, melanoma, triple negative breast cancer, PDR001, immunotherapy, head and neck scc, cervical scc, esophageal scc, lung scc
- Medical subject headings
- Pancreatic Neoplasms, Melanoma, Triple Negative Breast Neoplasms, Esophageal Squamous Cell Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LGK974Drug
Also called WNT974
PDR001Biological
| Study group | Role | What they receive |
|---|---|---|
| LGK974 | Experimental | LGK974 Receives: Drug: LGK974 |
| LGK974 in combination with PDR001 | Experimental | LGK in combination with PDR001 Receives: Drug: LGK974; 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) during the first cycle of LGK974 treatment and during the first 2 cycles of LGK974 in combination with PDR001
DLT is defined as an adverse event or abnormal laboratory value that is assessed by the investigator as unrelated to disease, disease progression, intercurrent illness, or concomitant medications and that meets the criteria defined in the study protocol.
The objective was to determine the Maximum Tolerated Dose (MTD) or Recommended Dose for Expansion (RDE) of LGK974 as a single agent and in combination with PDR001 when administered orally to adult patients with malignancies dependent on Wnt ligands.
Measured: 28 days (LGK974 single agent) and 56 days (LGK974 in combination with PDR001)
Secondary outcomes (5)
Type and category of study drug related adverse events (AE)
The incidence of treatment-emergent adverse events (new or worsening from baseline) will be summarized by primary system organ class, severity based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, type of AE, relationship to study drug by dose group.
Measured: 61 months
Absorption and plasma concentrations of LGK974
Evaluate pharmacokinetic (PK) parameters such as AUClast, AUCtau, Cmax, the apparent elimination T1/2 and Racc for LGK974 and its pharmacologically metabolite.
Measured: 61 months
PD related to the Wnt pathway
Assessing percent change from baseline to post-treatment of PD related to the Wnt pathway.
Measured: 61 months
Overall response rate of tumor
Patients with an Overall Response Rate(ORR), complete response (CR) or partial response (PR) rate and duration of response (DOR) assessed by RECIST 1.1 for single agent LGK974 and by RECIST1.1 and irRC for LGK974+PDR001.
Measured: 61 months
Absorportion and plasma concentrations of PDR001
Evaluate pharmacokinetic (PK) parameters such as AUClast, AUCtau, Cmax, the apparent elimination T1/2 and Racc for LGK974, its pharmacologically metabolite and PDR001.
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 posted10 May 2011 (estimated)
- Study start1 Dec 2011
- Primary completion1 Jun 2021
- Study completion17 Jun 2024
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 Pancreatic 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
- Single group
- Masking
- None (open label)
- Enrolment
- 185 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
- NCT01351103
- Sponsor's protocol ID
- CLGK974X2101
- Other IDs
- 2011-000495-33
- Status last verified
- Jun 2025
- First submitted
- 4 May 2011
- Last updated
- 13 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Rodon J, Argiles G, Connolly RM, Vaishampayan U, de Jonge M, Garralda E, Giannakis M, Smith DC, Dobson JR, McLaughlin ME, Seroutou A, Ji Y, Morawiak J, Moody SE, Janku F. Phase 1 study of single-agent WNT974, a first-in-class Porcupine inhibitor, in patients with advanced solid tumours. Br J Cancer. 2021 Jul;125(1):28-37. doi: 10.1038/s41416-021-01389-8. Epub 2021 May 3.
PubMed 33941878
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-label, Dose Escalation Study of Oral LGK974 in Patients With Malignancies Dependent on Wnt Ligands
- ClinicalTrials.gov ID
- NCT01351103
- Acronym / sponsor ID
- CLGK974X2101
- Conditions
- Pancreatic Cancer, BRAF Mutant Colorectal Cancer, Melanoma, Triple Negative Breast Cancer, Head and Neck Squamous Cell Cancer, Cervical Squamous Cell Cancer
- Keywords
- LGK974, pancreatic adenocarcinoma, BRAF mutant colorectal cancer, RNF43 mutation, RSPO fusion, melanoma, triple negative breast cancer, PDR001
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 185 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 1 Dec 2011 (actual)
- Primary completion
- 1 Jun 2021 (actual)
- Study completion
- 17 Jun 2024 (actual)
- First posted
- 10 May 2011 (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.
The primary purpose of this study was to find the recommended dose of LGK974 as a single agent and in combination with PDR001 that can be safely given to adult patients with selected solid malignancies that had progressed despite standard therapy or for which no effective standard therapy existed.
Detailed description
This open-label multicenter phase 1 dose escalation study was the first to administer LGK974 as a single agent or in combination with PDR001 in humans.
The study comprised of 2 parts: a dose escalation of LGK974 as a single agent, followed by a safety expansion in specific disease indications; and a dose escalation of LGK974 in combination with PDR001, followed by a safety expansion in cutaneous melanoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LGK974 | Experimental | Drug: LGK974LGK974 |
| LGK974 in combination with PDR001 | Experimental | Drug: LGK974, Biological: PDR001LGK in combination with 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)
- Diagnosis of locally advanced or metastatic cancer that has progressed despite standard therapy or for which no effective standard therapy exists and histological confirmation of one of the following diseases indicated below:
- Single Agent Dose escalation part:documented B-RAF mutant colorectal cancer or pancreatic adenocarcinoma. In addition, tumors of any histological origin with documented genetic alterations upstream in the Wnt signaling pathway are eligible with prior agreement with Novartis.
- Single Agent Dose expansion part: documented B-RAF mutant colorectal cancer with documented RNF43 mutation and/or RSPO fusion or pancreatic adenocarcinoma with documented RNF43 mutation. In addition, patients with tumors of any histological origin with documented genetic alterations upstream in the Wnt signaling pathway (e.g. RNF43 or RSPO fusion) are eligible with prior agreement with Novartis
- LGK974 with PDR001: Dose escalation: patients with the following cancers that were previously treated with anti-PD-1 therapy and whose best response on that therapy was progressive disease (i.e. primary refractory): melanoma, lung SCC, HNSCC. Patients with esophageal SCC, cervical SCC or TNBC who are either naïve or primary refractory to prior anti-PD-1 therapy.
- cutaneous melanoma that was primary refractory to prior anti-PD-1 therapy, defined as a best response of progressive disease or stable disease for <= 4 months, or disease recurrence with the first 6 months of adjuvant therapy. Patients with BRAF V600-mutant melanoma must have also received and been failed by prior systemic therapy with BRAF V600 inhibitor, with or without a MEK inhibitor.
Key exclusion criteria (10 listed)
- Impaired cardiac function
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of LGK974 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
- Brain metastases that have not been adequately treated
- Malignant disease other than that being treated in this study
- Laboratory abnormalities as specified in the protocol
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 |
|---|---|---|
| LGK974Also: WNT974 | Drug | LGK974, LGK974 in combination with PDR001 |
| PDR001 | Biological | LGK974 in combination with PDR001 |
Primary outcome
Incidence of dose limiting toxicities (DLTs) during the first cycle of LGK974 treatment and during the first 2 cycles of LGK974 in combination with PDR001
Time frame: 28 days (LGK974 single agent) and 56 days (LGK974 in combination with PDR001)
DLT is defined as an adverse event or abnormal laboratory value that is assessed by the investigator as unrelated to disease, disease progression, intercurrent illness, or concomitant medications and that meets the criteria defined in the study protocol. The objective was to determine the Maximum Tolerated Dose (MTD) or Recommended Dose for Expansion (RDE) of LGK974 as a single agent and in combination with PDR001 when administered orally to adult patients with malignancies dependent on Wnt ligands.
5 secondary outcomes
Type and category of study drug related adverse events (AE)
Time frame: 61 months
Absorption and plasma concentrations of LGK974
Time frame: 61 months
PD related to the Wnt pathway
Time frame: 61 months
Overall response rate of tumor
Time frame: 61 months
Absorportion and plasma concentrations of PDR001
Time frame: 61 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 13 Jun 2025.
- Derived from this study: PubMed 33941878Rodon J, Argiles G, Connolly RM, Vaishampayan U, de Jonge M, Garralda E, Giannakis M, Smith DC, Dobson JR, McLaughlin ME, Seroutou A, Ji Y, Morawiak J, Moody SE, Janku F. Phase 1 study of single-agent WNT974, a first-in-class Porcupine inhibitor, in patients with advanced solid tumours. Br J Cancer. 2021 Jul;125(1):28-37. doi: 10.1038/s41416-021-01389-8. Epub 2021 May 3.
- Link to Study ResultsLink 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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
20 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LGK974 and PDR001 in people with Pancreatic Cancer and BRAF Mutant Colorectal Cancer, run by Novartis Pharmaceuticals at 20 sites in 7 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 10 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 13 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in Spain, United States, Italy, Netherlands, Canada and 2 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 dose limiting toxicities (DLTs) during the first cycle of LGK974 treatment and during the first 2 cycles of LGK974 in combination with PDR001 (time frame: 28 days (LGK974 single agent) and 56 days (LGK974 in combination with PDR001)). 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 NCT01351103, 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 13 Jun 2025.