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, Michael; Meniawy, Tarek; Markman, Ben; Mileshkin, Linda; Harnett, Paul; Millward, Michael; Lundy, Joanne; Freimund, Alison; Norris, Christie; Mu, Song; Wu, John; Paton, Virginia; Gao, Bo

doi:10.1016/s1470-2045(19)30396-1

Cited by 92 publications

(83 citation statements)

References 20 publications

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“…Results from a Phase I study were 49 patient's suffering from solid tumors were treated with a combination of a PARPi and Tislelizumab showed 20% of patients achieved an objective response. Furthermore, 32% of patients entered a state of stable disease, where the tumor did not show any increase in size (Friedlander et al, 2019).…”

Section: Parp Inhibitors and Immunotherapymentioning

confidence: 98%

PARP Inhibitors: Clinical Relevance, Mechanisms of Action and Tumor Resistance

Rose

Burgess

O’Byrne

et al. 2020

Front. Cell Dev. Biol.

396

296

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The Poly (ADP-ribose) polymerase (PARP) family has many essential functions in cellular processes, including the regulation of transcription, apoptosis and the DNA damage response. PARP1 possesses Poly (ADP-ribose) activity and when activated by DNA damage, adds branched PAR chains to facilitate the recruitment of other repair proteins to promote the repair of DNA single-strand breaks. PARP inhibitors (PARPi) were the first approved cancer drugs that specifically targeted the DNA damage response in BRCA1/2 mutated breast and ovarian cancers. Since then, there has been significant advances in our understanding of the mechanisms behind sensitization of tumors to PARP inhibitors and expansion of the use of PARPi to treat several other cancer types. Here, we review the recent advances in the proposed mechanisms of action of PARPi, biomarkers of the tumor response to PARPi, clinical advances in PARPi therapy, including the potential of combination therapies and mechanisms of tumor resistance.

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Section: Parp Inhibitors and Immunotherapymentioning

confidence: 98%

PARP Inhibitors: Clinical Relevance, Mechanisms of Action and Tumor Resistance

Rose

Burgess

O’Byrne

et al. 2020

Front. Cell Dev. Biol.

396

296

View full text Add to dashboard Cite

show abstract

“…The recommended phase 2 dose was determined as tislelizumab 200 mg every 3 weeks in combination with pamiparib 40 mg twice daily. Pamiparib plus tislelizumab exhibited generally well tolerance and were associated with anti-tumor responses and clinical benefit in patients with advanced solid tumors, supporting further investigation of the combined therapy (Friedlander et al, 2019).…”

Section: Tislelizumab Based Combinational Therapymentioning

confidence: 76%

PD-1/PD-L1 Based Combinational Cancer Therapy: Icing on the Cake

Zhang

Yan

et al. 2020

Front. Pharmacol.

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Cancer has been a major global health problem due to its high morbidity and mortality. While many chemotherapy agents have been studied and applied in clinical trials or in clinic, their application is limited due to its toxic side effects and poor tolerability. Monoclonal antibodies specific to the PD-1 and PD-L1 immune checkpoints have been approved for the treatment of various tumors. However, the application of PD-1/PD-L1 inhibitors remains suboptimal and thus another strategy comes in to our sight involving the combination of checkpoint inhibitors with other agents, enhancing the therapeutic efficacy. Various novel promising approaches are now in clinical trials, just as icing on the cake. This review summarizes relevant investigations on combinatorial therapeutics based on PD-1/PD-L1 inhibition.

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“…The combination of tislelizumab with a novel PARP inhibitor-pamiparib was evaluated in solid tumors in a phase Ia/b clinical trial. Ten (20%) of 49 patients achieved an objective response, including two complete responses and eight partial responses (21).…”

Section: Discussionmentioning

confidence: 99%

Case Report: Double Germline Mutations in BRCA1 and MSH2 in a Patient With Mixed Serous-Endometrioid Endometrial Carcinoma

Zheng

Yuan

et al. 2020

Front. Med.

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Mixed serous-endometrioid endometrial carcinoma is a type of endometrial cancer with relatively low incidence. The genetic factors contributing to the tumorigenesis of mixed carcinoma remains to be explored. Here, we report the first identification of two germline mutations in BRCA1 and MSH2 in a woman with mixed serous papillary adenocarcinoma and endometrioid carcinoma. Immunohistochemistry analysis showed loss of MSH2 and MSH6 protein expression in the endometrioid component. The patient showed partial response to tislelizumab treatment following progression on chemotherapy. Two germline mutations in BRCA1 and MSH2 may collectively promote the tumorigenesis of uterine endometrium with two distinct histological components.

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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

Cited by 92 publications

References 20 publications

PARP Inhibitors: Clinical Relevance, Mechanisms of Action and Tumor Resistance

PARP Inhibitors: Clinical Relevance, Mechanisms of Action and Tumor Resistance

PD-1/PD-L1 Based Combinational Cancer Therapy: Icing on the Cake

Case Report: Double Germline Mutations in BRCA1 and MSH2 in a Patient With Mixed Serous-Endometrioid Endometrial Carcinoma

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