Tislelizumab + Pamiparib for Cancer

Recruiting at 170 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: BeiGene

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

430 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open-label, multicenter, extension study to evaluate the long-term safety and efficacy of BeiGene investigational drugs in participants with advanced malignancies who participated in a prior BeiGene-sponsored clinical study (parent study).

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.

What data supports the effectiveness of the drug combination of Tislelizumab and Pamiparib for cancer?

Research shows that combining pamiparib, a drug that helps repair damaged DNA, with tislelizumab, a drug that helps the immune system fight cancer, has shown antitumor activity in patients with advanced solid tumors. Additionally, similar drugs like atezolizumab have been effective in treating certain types of breast cancer, suggesting potential benefits of this combination. ^{1 2 3 4 5}

Is the combination of Tislelizumab and Pamiparib safe for humans?

Studies have shown that the combination of Tislelizumab and Pamiparib has been tested for safety in patients with advanced solid tumors. The research indicates that this combination is generally safe, but like all treatments, it may have side effects, which were monitored during the trials. ^{1 2 5 6 7}

What makes the drug combination of pamiparib and tislelizumab unique for treating advanced solid tumors?

The combination of pamiparib, a PARP inhibitor that helps repair damaged DNA in cancer cells, and tislelizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, is unique because it targets both the cancer cells' DNA repair mechanisms and the immune system's ability to recognize and destroy cancer cells, offering a novel approach for treating advanced solid tumors. ^{1 2 3 4 8}

Research Team

Study Director

Principal Investigator

BeiGene

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. 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]

2. England 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. [2020]

3. 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]

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

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

5. Netherlands 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. [2023]

6. England 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. [2023]

7. 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]

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

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