Solid TumorsPhase 1NCT03301896
Study of the Safety and Efficacy of LHC165 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies
A Phase 1 study testing LHC165 and PDR001 in people with Solid Tumors, run by Novartis Pharmaceuticals at 9 sites in 7 countries.
Trial summary
The purpose of this trial was to explore the clinical utility of two investigational agents in patients with advanced cancer. This was a multi-center, open-label Phase I/Ib study. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors
- What is being tested?
- LHC165 and PDR001
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 9 sitesin 7 countries
- Study dates
- 31 Jan 2018to 30 Jun 2022
- 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 procedures unless considered standard of care.
- Adult men and women (≥ 18 years of age) with histologically confirmed diagnosis of metastatic and/or advanced solid tumors not amenable to curative treatment by surgery.
- Patients must be willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
- Dose escalation: Patients with accessible tumors and with measurable disease as determined by RECIST 1.1 and have progressed despite standard treatment or are intolerant of standard treatment, or for whom no standard treatment exists.
- Dose expansion: Patients with advanced/metastatic solid tumors: HNSCC, melanoma, accessible tumors and visceral tumors (LHC165 combination with PDR001 only). Patients must have measurable disease as determined by RECIST 1.1 and have progressed despite standard treatment or are intolerant to standard treatment, or for whom no standard treatment exists• Patients must have at least two sites of disease amenable to biopsy.
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
Who cannot join
- Presence of symptomatic or uncontrolled central nervous system (CNS) metastases requiring local CNS-directed treatment.
- Patients diagnosed with hematological malignancies.
- Patients with prior stem cell transplants.
- Patients previously treated with TLR-7/8 agonist treatment.
- History of primary immunodeficiency
- Patients who discontinued prior anti-PD-1/PD-L1 therapy due to an anti-PD-1/PD-L1-related toxicity.
- Malignant disease, other than that being treated in this study
Trial locations and contacts
9 sites in 7 countries.
9 sites in 7 countries
United States2 sites
MD Anderson Cancer Center
Houston, Texas, 77030
UCLA
Los Angeles, California, 90095
Spain2 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Madrid, 28009
About this study
Official title: A Phase I/Ib, Open-label, Multi-center Dose-escalation and Dose-expansion Study of the Safety and Tolerability of Intra-tumorally Administered LHC165 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies
The purpose of this trial was to explore the clinical utility of two investigational agents in patients with advanced cancer.
This was a multi-center, open-label Phase I/Ib study. The primary objectives of the trial were:
- To characterize the safety and tolerability of intratumoral LHC165 in patients with solid tumors as a single agent and in combination with PDR001
- To determine and evaluate the maximum tolerated dose (MTD)/recommended dose (RD) for LHC165 as a single agent and in combination with PDR001
Read the detailed description
This was a multi-center, open-label Phase I/Ib study. The study consisted of four dose escalation parts and two dose expansion parts testing LHC165 as a single agent or LHC165 in combination with PDR001. The dose escalation parts estimated the Maximum Tolerated Dose (MTD) and/or Recommended Dose for Expansion (RDE) and were planned to test two different dosing schedules for LHC165 single agent (Group A and B) and LHC165 in combination with PDR001 (Group C and D).
The dose expansion parts of the study were planned to use the MTD/RDE for each the LHC165 single agent (Group E) and LHC165 in combination with PDR001 (Group F), determined in the respective dose escalation parts to assess the activity, safety and tolerability of LHC165 as a single agent or LHC165 in combination with PDR001 in patients with specific types of solid tumors.
The study was terminated due to business reasons. Groups B, D and E were not opened for enrollment.
- Conditions
- Solid Tumors
- Being tested
- LHC165, PDR001
- Keywords
- Phase I, LHC165, PDR001, intratumoral injection, abscopal, checkpoint inhibitor, programmed cell death, PD-1, TLR-7, toll-like receptor, melanoma, head and neck
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LHC165Drug
LHC165 intratumoral injection
PDR001Biological
PDR001 infusion
| Study group | Role | What they receive |
|---|---|---|
| LHC165 single agent | Experimental | LHC165 intratumoral injection given alone Receives: Drug: LHC165 |
| LHC165 in combination with PDR001 | Experimental | LHC165 intratumoral injection given with PDR001 infusion Receives: Drug: LHC165; Biological: PDR001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Escalation: Incidence of Dose-limiting Toxicities (DLTs) in Cycle 1
Dose Limiting Toxicity Evaluation Period
Measured: day 28
Escalation and Expansion: Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs), including changes in laboratory parameters, vital signs, electrocardiograms (ECGs)
Measured: 24 months
Secondary outcomes (16)
Objective Response Rate (ORR) per RECIST 1.1 and iRECIST
Measured: 24 months
Best Overall Response (BOR) per RECIST 1.1 and iRECIST
Measured: 24 months
Progression-Free Survival (PFS) per RECIST 1.1 and iRECIST
Measured: 24 months
Duration of Response (DOR) per RECIST 1.1 and iRECIST
Measured: 24 months
Disease Control Rate (DCR) per RECIST 1.1 and iRECIST
Measured: 24 months
Serum concentration profiles of LHC165 as a single agent: Cmax
Measured: 24 months
Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: Cmax
Measured: 24 months
Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: Cmax
Measured: 24 months
Serum concentration profiles of LHC165 as a single agent: AUC
Measured: 24 months
Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: AUC
Measured: 24 months
Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: AUC
Measured: 24 months
Serum concentration profiles of LHC165 as a single agent: Tmax
Measured: 24 months
Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: Tmax
Measured: 24 months
Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: Tmax
Measured: 24 months
Presence and titer of anti-PDR001 antibodies
Measured: 24 months
Change from baseline in tumor infiltrating lymphocytes in injected and distal tumor specimens
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2017
- Study start31 Jan 2018
- Primary completion30 Jun 2022
- Study completion30 Jun 2022
Why it stopped: Business reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorsStudies 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
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Nehal Parikh, MD, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03301896
- Sponsor's protocol ID
- CLHC165X2101
- Status last verified
- Jun 2024
- First submitted
- 29 Sep 2017
- Last updated
- 20 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2024. 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 and Dose-expansion Study of the Safety and Tolerability of Intra-tumorally Administered LHC165 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies
- ClinicalTrials.gov ID
- NCT03301896
- Acronym / sponsor ID
- CLHC165X2101
- Conditions
- Solid Tumors
- Keywords
- Phase I, LHC165, PDR001, intratumoral injection, abscopal, checkpoint inhibitor, programmed cell death, PD-1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business reasons
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 31 Jan 2018 (actual)
- Primary completion
- 30 Jun 2022 (actual)
- Study completion
- 30 Jun 2022 (actual)
- First posted
- 4 Oct 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 trial was to explore the clinical utility of two investigational agents in patients with advanced cancer.
This was a multi-center, open-label Phase I/Ib study. The primary objectives of the trial were:
- To characterize the safety and tolerability of intratumoral LHC165 in patients with solid tumors as a single agent and in combination with PDR001
- To determine and evaluate the maximum tolerated dose (MTD)/recommended dose (RD) for LHC165 as a single agent and in combination with PDR001
Detailed description
This was a multi-center, open-label Phase I/Ib study. The study consisted of four dose escalation parts and two dose expansion parts testing LHC165 as a single agent or LHC165 in combination with PDR001. The dose escalation parts estimated the Maximum Tolerated Dose (MTD) and/or Recommended Dose for Expansion (RDE) and were planned to test two different dosing schedules for LHC165 single agent (Group A and B) and LHC165 in combination with PDR001 (Group C and D).
The dose expansion parts of the study were planned to use the MTD/RDE for each the LHC165 single agent (Group E) and LHC165 in combination with PDR001 (Group F), determined in the respective dose escalation parts to assess the activity, safety and tolerability of LHC165 as a single agent or LHC165 in combination with PDR001 in patients with specific types of solid tumors.
The study was terminated due to business reasons. Groups B, D and E were not opened for enrollment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LHC165 single agent | Experimental | Drug: LHC165LHC165 intratumoral injection given alone |
| LHC165 in combination with PDR001 | Experimental | Drug: LHC165, Biological: PDR001LHC165 intratumoral injection given with PDR001 infusion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Written informed consent must be obtained prior to any procedures unless considered standard of care.
- Adult men and women (≥ 18 years of age) with histologically confirmed diagnosis of metastatic and/or advanced solid tumors not amenable to curative treatment by surgery.
- Patients must be willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
- Dose escalation: Patients with accessible tumors and with measurable disease as determined by RECIST 1.1 and have progressed despite standard treatment or are intolerant of standard treatment, or for whom no standard treatment exists.
- Dose expansion: Patients with advanced/metastatic solid tumors: HNSCC, melanoma, accessible tumors and visceral tumors (LHC165 combination with PDR001 only). Patients must have measurable disease as determined by RECIST 1.1 and have progressed despite standard treatment or are intolerant to standard treatment, or for whom no standard treatment exists• Patients must have at least two sites of disease amenable to biopsy.
Key exclusion criteria (7 listed)
- Presence of symptomatic or uncontrolled central nervous system (CNS) metastases requiring local CNS-directed treatment.
- Patients diagnosed with hematological malignancies.
- Patients with prior stem cell transplants.
- Patients previously treated with TLR-7/8 agonist treatment.
- History of primary immunodeficiency
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 |
|---|---|---|
| LHC165LHC165 intratumoral injection | Drug | LHC165 in combination with PDR001, LHC165 single agent |
| PDR001PDR001 infusion | Biological | LHC165 in combination with PDR001 |
Primary outcome
Escalation: Incidence of Dose-limiting Toxicities (DLTs) in Cycle 1
Time frame: day 28
Dose Limiting Toxicity Evaluation Period
Escalation and Expansion: Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs), including changes in laboratory parameters, vital signs, electrocardiograms (ECGs)
Time frame: 24 months
16 secondary outcomes
Objective Response Rate (ORR) per RECIST 1.1 and iRECIST
Time frame: 24 months
Best Overall Response (BOR) per RECIST 1.1 and iRECIST
Time frame: 24 months
Progression-Free Survival (PFS) per RECIST 1.1 and iRECIST
Time frame: 24 months
Duration of Response (DOR) per RECIST 1.1 and iRECIST
Time frame: 24 months
Disease Control Rate (DCR) per RECIST 1.1 and iRECIST
Time frame: 24 months
Serum concentration profiles of LHC165 as a single agent: Cmax
Time frame: 24 months
Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: Cmax
Time frame: 24 months
Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: Cmax
Time frame: 24 months
Serum concentration profiles of LHC165 as a single agent: AUC
Time frame: 24 months
Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: AUC
Time frame: 24 months
Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: AUC
Time frame: 24 months
Serum concentration profiles of LHC165 as a single agent: Tmax
Time frame: 24 months
Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: Tmax
Time frame: 24 months
Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: Tmax
Time frame: 24 months
Presence and titer of anti-PDR001 antibodies
Time frame: 24 months
Change from baseline in tumor infiltrating lymphocytes in injected and distal tumor specimens
Time frame: 24 months
Results and safety
The study was stopped early (reason given: Business reasons). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2024.
- Study ResultsLink provided by the sponsor.
- Plain Language Trial SummaryLink 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.
Nehal Parikh, MD study director
Novartis Pharmaceuticals
9 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 LHC165 and PDR001 in people with Solid Tumors, run by Novartis Pharmaceuticals at 9 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 6 inclusion and 7 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 20 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Spain, Belgium, Germany, Italy 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 was stopped early (reason given: Business reasons). 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?
Escalation: Incidence of Dose-limiting Toxicities (DLTs) in Cycle 1 (time frame: day 28). 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?
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 20 Jun 2024.