KFA115 + Tislelizumab for Advanced Cancers

Recruiting at 27 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Novartis Pharmaceuticals

Must not be taking: QT-prolonging agents

Disqualifiers: Cardiac disease, Autoimmune disease, ILD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and optimal dose of KFA115 (an experimental treatment) alone or combined with pembrolizumab for certain advanced cancers. The study targets non-small cell lung cancer, renal cell carcinoma, cutaneous melanoma, ovarian cancer, nasopharyngeal carcinoma, and other specific cancers. It seeks participants whose disease has progressed after initial treatments. This trial may suit individuals who have tried previous therapies but continue to experience disease advancement. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use drugs that prolong the QT interval (a heart rhythm measure) unless you can stop them for the study duration.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have examined the safety of KFA115, both alone and with pembrolizumab. These studies aim to assess patient tolerance and determine the optimal dose. As this research is in its early stages, information on the safety of KFA115 remains limited. However, pembrolizumab is an FDA-approved treatment for other conditions, offering some reassurance about its safety when combined with KFA115. It is important to note that the current study, being in an early phase, primarily focuses on safety and patient tolerance. Researchers closely monitor any potential side effects and the body's reaction to the treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about KFA115 and Tislelizumab for advanced cancers because these treatments offer a fresh approach compared to existing options like chemotherapy and other immunotherapies. KFA115 is a novel compound that targets specific pathways involved in tumor growth, potentially offering a more tailored attack on cancer cells. Tislelizumab, a PD-1 inhibitor, works by boosting the immune system's ability to detect and destroy cancer cells, offering a complementary mechanism to KFA115. The combination of these treatments might provide a more powerful and precise way to tackle advanced cancers, sparking hope for improved outcomes.

What evidence suggests that this trial's treatments could be effective for advanced cancers?

Research has shown that KFA115, a new treatment tested in this trial, targets specific proteins that aid cancer cell growth. Early results suggest that KFA115 alone, which participants may receive as monotherapy, shows promise in fighting advanced cancers by interfering with these proteins. In this trial, KFA115 is also tested in combination with pembrolizumab, an existing cancer treatment, which might further enhance the immune system's ability to fight cancer. Tislelizumab, another treatment option in this trial, blocks certain pathways that cancer uses to evade the immune system. While detailed information on KFA115’s effectiveness is still being gathered, these methods offer hope as a powerful new tool in cancer treatment. ^{1 2 3 4 6}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced cancers like renal cell carcinoma, ovarian cancer, melanoma, and non-small cell lung cancer. Participants must have tried some treatments already and meet specific medical history criteria. They should weigh over 36 kg and be able to undergo a tumor biopsy.

Inclusion Criteria

I have melanoma that worsened after anti-PD(L)1 therapy and, if BRAF V600 mutant, was also treated with a BRAF inhibitor.

My lung cancer responded to previous immunotherapy for at least 4 months and I've had platinum-based chemotherapy.

I am willing and able to have a biopsy as per my hospital's rules.

Exclusion Criteria

I have never had lung inflammation or similar lung issues that needed strong steroids.

I can stop taking medications that affect my heart's rhythm for the study.

History of severe hypersensitivity reactions to any ingredient of study drug(s) and other mAbs and/or their excipients.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Characterization of safety and tolerability of KFA115 and KFA115 in combination with pembrolizumab to determine the maximum tolerated dose (MTD) or recommended dose (RD)

28 days

Dose Expansion

Assessment of preliminary anti-tumor activity and further safety and tolerability at MTD/RD in defined patient populations

35 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• KFA115
• Tislelizumab

Trial Overview The study tests the safety and effectiveness of KFA115 alone or combined with tislelizumab in treating select advanced cancers. It aims to find the highest dose patients can tolerate without severe side effects.

How Is the Trial Designed?

Group I: Single-agent KFA115 Experimental Treatment 1 Intervention

KFA115 monotherapy

Group II: KFA115 run-in (1 cycle) + pembrolizumab Experimental Treatment 2 Interventions

1-cycle KFA115 run-in followed by addition of pembrolizumab

Group III: KFA115 + pembrolizumab Experimental Treatment 2 Interventions

KFA115 + pembrolizumab combination given concurrently

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

Tislelizumab is a modified PD-1 antibody that effectively inhibits tumor growth in various cancers, including Hodgkin's lymphoma and lung cancer, and has received multiple approvals in China for its use.

It has a favorable safety profile with common side effects like fatigue and anemia, and it offers economic advantages over other PD-1 inhibitors, making it a promising option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab: A Modified Anti-tumor Programmed Death Receptor 1 Antibody. Zhang, L., Geng, Z., Hao, B., et al.[2023]

Tislelizumab, an anti-PD-1 monoclonal antibody, showed a confirmed objective response rate of 24% in patients with PD-L1-positive urothelial carcinoma who had progressed after platinum therapy, indicating its efficacy in this challenging patient population.

The treatment had a manageable safety profile, with the most common adverse events being anemia (27%) and pyrexia (19%), and only a small percentage of patients experiencing severe side effects, suggesting that tislelizumab is a viable option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab in Asian patients with previously treated locally advanced or metastatic urothelial carcinoma. Ye, D., Liu, J., Zhou, A., et al.[2022]

In a phase 3 trial involving 332 patients with advanced nonsquamous non-small cell lung cancer (nsq-NSCLC), the combination of tislelizumab and chemotherapy significantly improved progression-free survival (PFS) compared to chemotherapy alone, with a median PFS of 9.7 months versus 7.6 months.

The addition of tislelizumab also resulted in higher response rates and longer duration of response, making it a promising first-line treatment option for patients with advanced nsq-NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab Plus Chemotherapy as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC (RATIONALE 304): A Randomized Phase 3 Trial. Lu, S., Wang, J., Yu, Y., et al.[2021]

In a study of 223 patients with locally advanced/metastatic non-squamous non-small cell lung cancer, 57.4% achieved an objective tumor response when treated with tislelizumab combined with chemotherapy, with a median time to response of 7.9 weeks.

The treatment was generally well tolerated, and responders who achieved deeper tumor shrinkage (greater than 30%) showed a trend toward longer progression-free survival, indicating both efficacy and safety of tislelizumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Response characteristics of tislelizumab combined with chemotherapy in first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer]. Lu, S., Yu, XM., Hu, YP., et al.[2023]

An indirect comparison of tislelizumab and pembrolizumab in combination with chemotherapy for advanced NSCLC, involving over 2,000 participants from 6 randomized trials, showed no significant differences in overall survival, progression-free survival, or objective response rates between the two treatments.

Both treatments were associated with a similar risk of severe adverse events, indicating that either tislelizumab or pembrolizumab can be considered effective and safe options for first-line therapy in advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab plus chemotherapy versus pembrolizumab plus chemotherapy for the first-line treatment of advanced non-small cell lung cancer: systematic review and indirect comparison of randomized trials. Guo, Y., Jia, J., Hao, Z., et al.[2023]

In a study involving 180 patients with advanced solid tumors, the combination of pamiparib and tislelizumab demonstrated an overall objective response rate (ORR) of 20%, with the highest response (47.4%) observed in patients with triple-negative breast cancer (TNBC) who had BRCA1/2 mutations or homologous recombination deficiency.

While the treatment showed promising antitumor activity, it was associated with a significant incidence of treatment-emergent adverse events, with 61.7% of patients experiencing grade 3 or higher side effects, indicating that while the therapy is effective, careful monitoring for safety is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pamiparib in combination with tislelizumab in patients with advanced solid tumours: results from the dose-expansion stage of a multicentre, open-label, phase I trial. Friedlander, M., Mileshkin, L., Lombard, J., et al.[2023]

Tislelizumab, a PD-1 inhibitor, significantly improved the overall response rate (ORR) and disease control rate (DCR) in patients with malignant solid tumors, with odds ratios of 2.59 and 1.78, respectively, based on a meta-analysis of seven phase III trials involving 3478 participants.

The treatment also demonstrated improved overall survival (OS) and progression-free survival (PFS), with hazard ratios of 0.71 and 0.68, indicating that tislelizumab is an effective option for patients with solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tislelizumab for malignant solid tumor: a systematic review and meta-analysis of phase III randomized trials. Abushanab, AK., Mustafa, MT., Mousa, MT., et al.[2023]

In a phase II study with 70 patients suffering from relapsed/refractory classical Hodgkin lymphoma, tislelizumab showed a high overall response rate of 87.1% and a complete response rate of 67.1% after a median follow-up of 33.8 months, indicating its efficacy as a treatment option.

The treatment demonstrated a favorable safety profile, with 97.1% of patients experiencing treatment-related adverse events, but only 31.4% having severe (grade ≥3) events, and just 8.6% discontinuing treatment due to adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab for Relapsed/Refractory Classical Hodgkin Lymphoma: 3-Year Follow-up and Correlative Biomarker Analysis. Song, Y., Gao, Q., Zhang, H., et al.[2023]

Tislelizumab is an anti-PD-1 monoclonal antibody developed as an immunotherapy for cancer, specifically approved in December 2019 in China for relapsed or refractory classical Hodgkin's lymphoma after at least two prior chemotherapy treatments.

The drug has shown promise in treating both hematological cancers and advanced solid tumors, indicating its potential for future approvals in additional cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab: First Approval. Lee, A., Keam, SJ.[2020]

Citations

1. novartis.com novartis.com/clinicaltrials/study/nct05544929

A Study of Safety and Efficacy of KFA115 Alone ... The purpose of this study is to characterize the safety and tolerability of KFA115 and KFA115 in combination with pembrolizumab in patients with select ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05544929

NCT05544929 | A Study of Safety and Efficacy of KFA115 ... 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 ...

3. clinicaltrial.be clinicaltrial.be/en/details/23093?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

A Study of Safety and Efficacy of KFA115 Alone and in Com... Discover the latest clinical trials, research studies, and groundbreaking medical advances with our comprehensive, user-friendly platform.

4. trialx.com trialx.com/clinical-trials/listings/241550/a-study-of-safety-and-efficacy-of-kfa115-alone-and-in-combination-with-pembrolizumab-in-patients-with-select-advanced-cancers/

A Study of Safety and Efficacy of KFA115 ... The purpose of this study is to characterize the safety and tolerability of KFA115 and KFA115 in combination with pembrolizumab in patients with ...

5. data.niaid.nih.gov data.niaid.nih.gov/resources?id=2748708

A Study of Safety and Efficacy of KFA115 Alone ... The purpose of this study is to characterize the safety and tolerability of KFA115 and KFA115 in combination with tislelizumab in patients with select ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05544929?term=AREA%5BConditionSearch%5D(Mesothelioma)%20AND%20AREA%5BMinimumAge%5D(RANGE%5BMIN,%2099%20Years%5D%20OR%20MISSING)%20AND%20AREA%5BMaximumAge%5D(RANGE%5B18%20Years,%20MAX%5D%20OR%20MISSING)%20AND%20AREA%5BStdAge%5DNOT%20MISSING%20AND%20SEARCH%5BLocation%5D(AREA%5BLocationCountry%5DGermany)%20AND%20AREA%5BOverallStatus%5D(RECRUITING)%20AND%20AREA%5BPhase%5D(PHASE1%20OR%20PHASE2%20OR%20PHASE3%20OR%20PHASE4)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)%20AND%20AREA%5BFunderTypeSearch%5D(INDUSTRY%20OR%20(OTHER_GOV%20OR%20INDIV%20OR%20NETWORK%20OR%20AMBIG%20OR%20OTHER%20OR%20UNKNOWN))&rank=3

A Study of Safety and Efficacy of KFA115 Alone ... 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 ...