Tislelizumab + Pamiparib for Cancer

Enrolling by invitation at 196 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: BeiGene

Must not be taking: Systemic anticancer

Disqualifiers: Uncontrolled infection, Life-threatening illness, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: up to 7 years

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to explore the long-term safety and effectiveness of two investigational drugs, Tislelizumab (an immunotherapy) and Pamiparib (a PARP inhibitor), in individuals with advanced cancers. Researchers are testing various combinations of these drugs with other medications to assess their combined effectiveness. Participants from a previous BeiGene-sponsored study who continue to benefit from the treatment may be suitable candidates. This trial is ideal for those managing advanced cancer who have experienced success with treatments in a related study. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer treatments.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It seems that you may continue with treatments from the parent study, but it's best to discuss your specific situation with the study team.

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

Research has shown that pamiparib and tislelizumab are generally safe when used alone or together. In studies, the combination of pamiparib and tislelizumab produced promising results for patients with advanced solid tumors. This combination was mostly well-tolerated and led to some positive responses in reducing tumors.

Pamiparib alone is also considered safe in ongoing studies. While it can cause skin reactions, it is mostly well-tolerated and has shown activity against tumors.

Tislelizumab by itself has a consistent safety record. Studies across different types of cancer support its use as a safe treatment. It is already approved in Europe for certain lung cancers, indicating its recognized safety.

In summary, both pamiparib and tislelizumab are considered safe based on past studies, with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Tislelizumab and Pamiparib for cancer treatment because it offers a unique approach compared to existing options. Tislelizumab is a PD-1 inhibitor that helps the immune system recognize and attack cancer cells more effectively. Pamiparib, on the other hand, is a PARP inhibitor that prevents cancer cells from repairing their DNA, leading to cell death. This dual-action strategy not only targets the cancer directly but also boosts the body's immune response, potentially leading to more effective and durable outcomes compared to the standard chemotherapy and radiation therapies.

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

Research has shown that combining pamiparib and tislelizumab yields promising results for treating advanced cancers. In this trial, participants may receive this combination, which has proven effective against hard-to-treat solid tumors, particularly in triple-negative breast cancer (TNBC). One study reported a high response rate of 87.1% in patients with relapsed or hard-to-treat classical Hodgkin lymphoma treated with tislelizumab. Another study found that tislelizumab increased the average survival time for patients with a specific cancer type by 3.5 months. Overall, these treatments offer significant benefits and could be a potential option for those with advanced cancers. ^{6 7 8 9 10}

Who Is on the Research Team?

Study Director

Principal Investigator

BeiGene

Are You a Good Fit for This Trial?

This trial is for patients with advanced malignancies who were previously in a BeiGene study and may benefit from continued treatment. It's not for those who had severe side effects, recent serious infections, or used other cancer treatments between studies. Pregnant women and individuals with life-threatening conditions are also excluded.

Inclusion Criteria

The doctor believes that you will still benefit from taking tislelizumab and pamiparib either alone or together.

I am allowed to take pamiparib for my solid tumor, except for GBM, if my doctor agrees.

Currently participating in a BeiGene-sponsored eligible parent study

Exclusion Criteria

I do not have an uncontrolled infection or one that needed IV drugs before the study.

I stopped tislelizumab or pamiparib treatment due to severe side effects, not following study procedures, or withdrawing consent.

I don't have any health issues that could risk my safety in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Tislelizumab, Pamiparib, and other investigational agents as part of the extension study

up to 7 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 7 years

What Are the Treatments Tested in This Trial?

Interventions

• Pamiparib
• Tislelizumab

Trial Overview The study tests long-term safety of Tislelizumab and/or Pamiparib alone or combined with other agents like Capecitabine, Temozolomide, etc., in participants with advanced cancers to see if they continue to help without causing new issues.

How Is the Trial Designed?

Group I: R - Tislelizumab and Surzebiclimab and LBL-007 Combination Therapy Experimental Treatment 3 Interventions

Group II: Q - Tislelizumab and LBL-007 Combination Therapy Experimental Treatment 2 Interventions

Group III: P - Tislelizumab and Zanidatamab Combination Therapy Experimental Treatment 2 Interventions

Group IV: O - Tislelizumab and Lenvatinib Combination Therapy Experimental Treatment 2 Interventions

Group V: N - Tislelizumab and BGB-15025 Combination Therapy Experimental Treatment 2 Interventions

Group VI: M - Tislelizumab and Surzebiclimab Combination Therapy Experimental Treatment 2 Interventions

Group VII: L - Tislelizumab and BGB-A445 Combination Therapy Experimental Treatment 2 Interventions

Group VIII: K - Tislelizumab and Fruquintinib Combination Therapy Experimental Treatment 2 Interventions

Group IX: J - Tislelizumab and BAT1706 Combination Therapy, or BAT1706 Monotherapy Experimental Treatment 2 Interventions

Group X: I - Tislelizumab and Ociperlimab Combination Therapy Experimental Treatment 2 Interventions

Group XI: H - Tislelizumab and Sitravatinib Combination Therapy Experimental Treatment 2 Interventions

Group XII: G - Tislelizumab and Pamiparib Combination Therapy Experimental Treatment 2 Interventions

Group XIII: F - Pamiparib and Temozolomide Combination Therapy Experimental Treatment 2 Interventions

Group XIV: E - Zanidatamab Monotherapy Experimental Treatment 1 Intervention

Group XV: D - BGB-15025 Monotherapy Experimental Treatment 1 Intervention

Group XVI: C - Sitravatinib Monotherapy Experimental Treatment 1 Intervention

Group XVII: B - Pamiparib Monotherapy Experimental Treatment 1 Intervention

Group XVIII: A - Tislelizumab Monotherapy Experimental Treatment 1 Intervention

Pamiparib is already approved in China for the following indications:

Approved in China as Pamiparib for:

• Ovarian cancer

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Published Research Related to This Trial

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]

Pamiparib demonstrated promising efficacy in treating locally advanced or metastatic HER2-negative breast cancer with deleterious or suspected deleterious BRCA1/2 mutations, achieving an objective response rate of 38.2% in triple-negative breast cancer and 61.9% in hormone receptor-positive cohorts.

The treatment was generally well-tolerated, although hematologic adverse events were common, leading to dose reductions in 64.8% of patients, indicating a need for monitoring but an overall acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pamiparib in patients with locally advanced or metastatic HER2-negative breast cancer with germline BRCA mutations: a phase II study. Xu, B., Sun, T., Shi, Y., et al.[2023]

Atezolizumab, combined with nab-paclitaxel, significantly improved progression-free survival in patients with advanced triple-negative breast cancer (TNBC) compared to placebo, based on the phase III IMpassion130 trial involving patients with unresectable locally advanced or metastatic TNBC.

While the combination therapy showed a tolerable safety profile, with common side effects like neutropenia and immune-related adverse events, it did not significantly affect health-related quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab (in Combination with Nab-Paclitaxel): A Review in Advanced Triple-Negative Breast Cancer. Kang, C., Syed, YY.[2020]

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 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]

In a phase I study involving 32 patients with advanced solid tumors, the combination of ociperlimab and tislelizumab was well tolerated, with no dose-limiting toxicities reported and a recommended phase II dose established at ociperlimab 900 mg plus tislelizumab 200 mg every 3 weeks.

Preliminary results showed an overall response rate of 10% and a disease control rate of 50%, indicating some antitumor activity, which supports further investigation in phase II/III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AdvanTIG-105: a phase I dose escalation study of the anti-TIGIT monoclonal antibody ociperlimab in combination with tislelizumab in patients with advanced solid tumors. Frentzas, S., Kao, S., Gao, R., et al.[2023]

The combination of pamiparib (a PARP inhibitor) and tislelizumab (an anti-PD-1 antibody) was generally well tolerated in a study of 49 patients with advanced solid tumors, with a recommended phase 2 dose established as tislelizumab 200 mg every 3 weeks plus pamiparib 40 mg twice daily.

Out of the participants, 20% achieved an objective response, including two complete responses, indicating that this combination therapy may provide clinical benefits and warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pamiparib in combination with tislelizumab in patients with advanced solid tumours: results from the dose-escalation stage of a multicentre, open-label, phase 1a/b trial. Friedlander, M., Meniawy, T., Markman, B., et al.[2020]

Citations

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Pamiparib in combination with tislelizumab in patients with ... Pamiparib plus tislelizumab showed a variable level of antitumour activity in patients with advanced solid tumours, with the highest ORR in TNBC and was ...

2. clinicaltrials.gov clinicaltrials.gov/show/NCT04985721

NCT04985721 | A Trial of Pamiparib With Tislelizumab in ... This study will describe the efficacy of pamiparib in combination with tislelizumab in patients with advanced tumours harbouring molecular profiles ...

3. withpower.com withpower.com/trial/tislelizumab-pamiparib-for-cancer-7067c

Tislelizumab + Pamiparib for Cancer · Info for Participants 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% ...

4. clin.larvol.com clin.larvol.com/trial-detail/NCT03430843

A Study of Tislelizumab (BGB-A317) Versus Chemotherapy ... In PD-L1 positive patients, tislelizumab extended median OS by 3.5 months with a 46% reduction in the risk of death (HR=0.54, 95% CI: 0.36-0.79, p=0.0006)...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1470204519303961

Pamiparib in combination with tislelizumab in patients ... Pamiparib with tislelizumab was generally well tolerated and associated with antitumour responses and clinical benefit in patients with advanced solid tumours.

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)58674-4/fulltext

Safety, antitumor activity, and pharmacokinetics (PK) of ... Pamiparib continues to be generally well tolerated and demonstrates antitumor activity in this update of an ongoing, phase 1 dose-escalation/expansion study.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0923753419586744

Safety, antitumor activity, and pharmacokinetics (PK) of ... Pamiparib continues to be generally well tolerated and demonstrates antitumor activity in this update of an ongoing, phase 1 dose-escalation/expansion study in ...

8. cdn.caymanchem.com cdn.caymanchem.com/cdn/msds/33182m.pdf

Safety Data Sheet Sensitization: Sensitization possible through skin contact. · Additional toxicological information: · Carcinogenic categories. · IARC ( ...

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Voskoboynik BGB-290 AU-002 ESMO ... Conclusions: Pamiparib continues to be generally well tolerated and demonstrates antitumor activity in this update of an ongoing, phase 1 dose-escalation/ ...

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NCT03333915 | Study of the Efficacy, Safety and ... This study is designed to evaluate the safety, tolerability, PKharmacokinetic profile and treatment effect of pamiparib in Chinese participants with ...