KFA115 + Tislelizumab for Advanced Cancers

Recruiting at21 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Novartis Pharmaceuticals

Must not be taking: QT-prolonging agents

Disqualifiers: Cardiac disease, Autoimmune disease, ILD, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests a new drug, KFA115, alone and with pembrolizumab in patients with advanced cancers. It aims to find the safest dose and see if the drugs can reduce tumors. The focus is on patients whose cancers are hard to treat with current options.

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.

What data supports the effectiveness of the drug KFA115 + Tislelizumab for advanced cancers?

Research shows that Tislelizumab, when combined with chemotherapy, can improve outcomes in patients with advanced non-small cell lung cancer and has shown promise in treating various other solid tumors. It has been approved for several cancer types in China and has demonstrated satisfactory anti-tumor effects, making it a potentially effective option for advanced cancers. ^{1 2 3 4 5}

Is the combination of KFA115 and Tislelizumab safe for humans?

Tislelizumab has been studied in various cancers and generally has an acceptable safety profile, with common side effects like fatigue and anemia. Serious side effects can include respiratory issues and liver problems, but these are less common. ^{2 3 6 7 8}

What makes the drug KFA115 + Tislelizumab unique for advanced cancers?

The combination of KFA115 and Tislelizumab is unique because Tislelizumab is a specially engineered antibody that blocks a protein called PD-1, which helps cancer cells hide from the immune system. This drug is designed to work better by reducing unwanted interactions with other immune cells, potentially offering a new option for treating various advanced cancers. ^{1 2 3 4 9}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• KFA115 (Other)
• Tislelizumab (Monoclonal Antibodies)

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.

Participant Groups

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

Findings from Research

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]

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 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, 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 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]

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]

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]

References

1. United States 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. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Tislelizumab: A Modified Anti-tumor Programmed Death Receptor 1 Antibody. [2023]

3. Switzerland 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. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Tislelizumab for Relapsed/Refractory Classical Hodgkin Lymphoma: 3-Year Follow-up and Correlative Biomarker Analysis. [2023]

5. England 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. [2023]

6. England 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. [2023]

7. China 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]. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Tislelizumab in Asian patients with previously treated locally advanced or metastatic urothelial carcinoma. [2022]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Tislelizumab: First Approval. [2020]