A Study of Safety and Efficacy of KFA115 Alone and in Combo With Pembrolizumab in Patients With Select Advanced Cancers

NCT05544929
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Phase
Phase 1
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Recruitment status
Active, not recruiting
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Participants
126
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Lead sponsor
Novartis Pharmaceuticals
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Start date
2022-10-26
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Number of sites
18
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Summary
The purpose of this study is to characterize the safety and tolerability of KFA115 and KFA115 in combination with pembrolizumab in patients with select advanced cancers, and to identify the maximum tolerated dose and/or recommended dose.
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Short title
A Study of Safety and Efficacy of KFA115 Alone and in Combo With Pembrolizumab in Patients With Select Advanced Cancers
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Official title
A Phase I, Open-label, Multi-center Study of KFA115 as a Single Agent and in Combination With Pembrolizumab in Patients With Select Advanced Cancers
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Active, not recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2027-10-05
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First posted
2022-09-19
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Registry last updated
2026-10-20
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Primary completion date
2027-10-05
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Start date
2022-10-26
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Actual participants
126
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Participants
126
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Participant count basis
Actual
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Protocol amendments
5
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Number of sites
18
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
Novartis Pharmaceuticals
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05544929
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ClinicalTrials.gov ID
NCT05544929
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Registry record
Open registry record
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Allocation
Not randomised
Model
Parallel groups
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Incidence and severity of dose limiting toxicities (DLTs) during the DLT evaluation period of single-agent KFA115 (dose escalation only)

    Timeframe: 28 days

    A DLT is defined as an adverse event or abnormal laboratory value that occurs during the DLT evaluation period where the relationship to study treatment cannot be ruled out, and is not primarily related to disease, disease progression, intercurrent illness, or concomitant medications and meets the criteria defined in the study protocol

  2. Incidence and severity of dose limiting toxicities (DLTs) during the DLT evaluation period of KFA115 in combination with pembrolizumab (dose escalation only)

    Timeframe: 28 days

    A DLT is defined as an adverse event or abnormal laboratory value that occurs during the DLT evaluation period where the relationship to study treatment cannot be ruled out, and is not primarily related to disease, disease progression, intercurrent illness, or concomitant medications and meets the criteria defined in the study protocol

  3. Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)

    Timeframe: 35 months

    Incidence and severity of adverse events and serious adverse events, including changes in laboratory values, vital signs, and electrocardiograms qualifying and reported as AEs

  4. Frequency of dose interruptions, reductions

    Timeframe: 35 months

    Number of dose interruptions of KFA115 and pembrolizumab, and number of dose reductions of KFA115

  5. Dose intensity

    Timeframe: 35 months

    Dose intensity of KFA115 and pembrolizumab is defined as the ratio of actual cumulative dose received and actual duration of exposure

  1. Best overall response (BOR) per RECIST v1.1

    Timeframe: 35 months

    BOR is defined as the best response recorded from the start of the treatment until disease progression/recurrence

  2. Progression free survival (PFS) per RECIST v1.1

    Timeframe: 35 months

    PFS is defined as 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

  3. Duration of response (DOR) per RECIST v1.1

    Timeframe: 35 months

    DOR is defined as the time from the date of the first documented response (CR or PR) to the date of the first documented progression as per RECIST v1.1 or death due to underlying cancer

  4. Time to progression (TTP) per RECIST v1.1

    Timeframe: 35 months

    TTP is defined as the time from date of start of treatment to the date of event defined as the first documented progression or death due to underlying cancer

  5. Area under the concentration time curve (AUC) of KFA115 or pembrolizumab

    Timeframe: During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab

    Area under the concentration time curve

  6. Peak plasma or serum concentration (Cmax) of KFA115 or pembrolizumab

    Timeframe: During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab

    The maximum (peak) observed plasma or serum drug concentration after single dose administration

  7. Minimum plasma or serum concentration (Cmin) of KFA115 or pembrolizumab

    Timeframe: During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab

    The minimum observed plasma or serum drug concentration reached during the time interval between two dose administrations

  8. Time to reach peak plasma or serum concentration (Tmax) of KFA115 or pembrolizumab

    Timeframe: During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab

    The time to reach maximum (peak) plasma or serum drug concentration after single dose administration

  9. Elimination half-life (T1/2) of KFA115 or pembrolizumab

    Timeframe: During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab

    The elimination half-life associated with the terminal slope of a semi logarithmic concentration-time curve

Sources for outcomes
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Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Maximum age
100 Years
Healthy volunteers
No

  • Non-small cell lung cancer with historic PD-L1 ≥ 1%, as determined locally using a clinically accepted assay. Patients must have experienced benefit from previous anti-PD(L)1-containing therapy for at least 4 months based on investigator-assessed disease stability or response prior to developing documented disease progression. Patients must have also received prior platinum-based chemotherapy, either in combination or in sequence with anti-PD-(L)1, unless patient was ineligible to receive such treatment.
  • Renal cell carcinoma, clear cell histology, previously treated with anti-PD(L)1-containing therapy and a VEGF targeted therapy as monotherapy or in combination. Patients should have documented disease progression following anti-PD(L)1-containing therapy.
  • Cutaneous melanoma, previously treated with anti-PD(L)1-containing therapy. Patients should have documented disease progression following anti-PD(L)1-containing therapy. Patients with BRAF V600-mutant melanoma must have also received prior therapy with a BRAF V600 inhibitor, with or without a MEK inhibitor.
  • Ovarian cancer, high-grade serous histology, naïve to anti-PD(L)1 therapy, must have received one prior systemic therapy in platinum-resistant setting.
  • Nasopharyngeal carcinoma, non-keratinizing locally advanced recurrent or metastatic. Depending on the study arm, patients may be naïve to anti-PD(L)1 therapy, or previously treated with platinum-based chemotherapy with or without anti-PD-(L)1.
  • Locally advanced unresectable or metastatic triple negative breast cancer, ovarian cancer (high-grade serous histology), anal cancer (squamous), MSI-H CRC, esophagogastric cancer, mesothelioma, and HNSCC.
  • Locally advanced unresectable or metastatic anal cancer (squamous), thymic carcinoma, MSI-H CRC, esophagogastric cancer, mesothelioma, and HNSCC, all naïve to anti-PD(L)1 therapy and for whom anti PD(L)1 therapy is not available.
  • Triple negative breast cancer with historic PD-L1 CPS ≥ 1%, must have received at least one line of chemotherapy. In addition, these patients must have previously received sacituzumab govitecan, and in the case of a BRCA mutation a PARP inhibitor, if these treatments are locally approved and accessible to the patient.

  • Impaired cardiac function or clinically significant cardiac disease.
  • Use of agents known to prolong the QT interval unless they can be permanently discontinued for the duration of study.
  • History of severe hypersensitivity reactions to any ingredient of study drug(s) and other mAbs and/or their excipients.
  • Active, known or suspected autoimmune disease. Patients with vitiligo, type I diabetes, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment or conditions not expected to recur may be considered. Patients previously exposed to anti-PD-1/PD-L1 treatment who are adequately treated for skin rash or with replacement therapy for endocrinopathies should not be excluded.
  • Any evidence of interstitial lung disease (ILD) or pneumonitis, or a prior history of ILD or non-infectious pneumonitis requiring high-dose glucocorticoids.
  • Patients who discontinued prior anti-PD-(L)1 therapy due to an anti-PD-(L)1-related toxicity (applicable to the KFA115 in combination with pembrolizumab treatment arms).
  • Patients with symptomatic peripheral neuropathy limiting instrumental activities of daily living.

Other protocol-defined inclusion/exclusion criteria may apply

Sources for eligibility
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  • Massachusetts General Hospital .Boston, United States
  • Massachusetts General HospitalBoston, United States
  • NYU School of MedicineNew York, United States
  • University of Pittsburgh Medical CenterPittsburgh, United States
  • SCRI Oncology PartnersNashville, United States
  • Novartis Investigative SiteToronto, Canada
  • Novartis Investigative SiteGuangzhou, China
  • Novartis Investigative SiteBeijing, China
  • Novartis Investigative SiteLyon, France
  • Novartis Investigative SiteDresden, Germany
  • Novartis Investigative SiteEssen, Germany
  • Novartis Investigative SiteHong Kong, Hong Kong
  • Novartis Investigative SiteMilan, Italy
  • Novartis Investigative SiteChuo Ku, Japan
  • Novartis Investigative SiteSingapore, Singapore
  • Novartis Investigative SiteSeoul, South Korea
  • Novartis Investigative SiteBarcelona, Spain
  • Novartis Investigative SiteTaipei, Taiwan
Sources for sites
clinicaltrials.gov

Other registry identifiers

  • 2022-502381-25
Sources for references
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)

Conditions (26)

Targets (1)