Pembrolizumab and Olaparib in Recurrent/Metastatic, Platinum Resistant Nasopharyngeal Cancer

Who is this study for? Patients with recurrent/metastatic, platinum resistant nasopharyngeal cancer
What treatments are being studied? Pembrolizumab
Status: Recruiting
Location: See location...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 2
SUMMARY

Recurrence rate after curative treatment for locally advanced Nasopharyngeal carcinoma (NPC) is reported varying from 15% to 30% of cases, while approximately 5-11% of patients present with de novo metastatic disease. In NPC, the immunogenicity of the cancer cell is derived from accumulated somatic mutations, but also from genomic and proteomic differences between host and Epstein Barr Virus (EBV). However, anti-cancer immune response tends to be feeble. This impaired anti-cancer immunity could be attributed to multiple factors including strategies to escape anti-cancer immunity. One of this is switch to immunosuppressive microenvironment, as well as aberrant negative co-stimulatory signals like PD-L1, that is over expressed in NPC. In 2017, the landmark KEYNOTE-028 trial firstly reported promising antitumor activities and safety profiles of pembrolizumab in previously treated RM-NPC Overall, after the treatment of PD-1 inhibitors, about 25% and 60% of the recurrent or metastatic nasopharyngeal carcinoma patients achieved ORR and DCR, respectively, with a profile of toxicities in line with the use of immune checkpoint inhibitors in other diseases. Recently, it was found that some non-BRCA-mutated tumors often harbor other alterations in HR genes except for germline BRCA deleterious mutations, thus making these tumors could benefit from PARPi treatment. PARP could contribute to resistance to chemotherapy induced DNA damage, NPC cell platinum resistant could use PARP to repair and escape apoptosis. In nasopharyngeal carcinoma PARP1 is overexpressed in comparison with normal nasopharyngeal cells, LMP1 (latent membrane protein one) activates PARP1 and increases Poly(ADP-ribos)ylation (PARylation) through PARP1. A preclinical study demonstrates that LMP1+ cells are more sensitive to PARP1 inhibition. After receiving PARPi treatment, accumulated chromosome rearrangements generate plenty of neoantigens and elevate the immunogenicity of tumor, PARPi-mediated acute inflammation remodels tumor immune microenvironment and drives a systemic Th1-skewing immune response. Patients in the POINT trial will receive pembrolizumab 200 mg intravenously (IV) on Day 1 of every 3-week dosing cycle (Q3W) and olaparib 300 mg capsules twice a day (BID) every day starting from Day 1 of Cycle 1. Treatment with protocol therapy will continue until objective disease progression, any prohibitive toxicity or until a maximum of 35 treatment cycles (up to 2 years).

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Male/female participants who are at least 18 years old

• The participant (or legally acceptable representative) provides written informed consent.

• Histologically confirmed diagnosis of nasopharyngeal carcinoma.

• Disease not amenable of surgical resection or irradiation with curative intent.

• Disease progressing within 6 months since previous platinum-based systemic treatment (as concomitant to RT or as first line treatment for RM NPC).

• Male participants:

• A male participant must agree to use contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 3 months after the last dose of study treatment and refrain from donating sperm during this period. Female partners of male patients should also use a highly effective form of contraception if they are of childbearing potential.

• Female participants:

• A female participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 4 months after the last dose of study treatment.

• A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:

⁃ Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR

⁃ A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 4 months after the last dose of study treatment.

• Measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the start of study treatment.

⁃ Patients must have a life expectancy ≥ 16 weeks.

⁃ Adequate organ function as defined in the following table (Table 5.1). Specimens must be collected within 10 days prior to the start of study treatment.

Locations
Other Locations
Italy
Asst Degli Spedali Civili Di Brescia
RECRUITING
Brescia
Contact Information
Primary
Paolo Bossi, MD
paolo.bossi@unibs.it
+390303998969
Time Frame
Start Date: 2022-03-24
Estimated Completion Date: 2028-03-24
Participants
Target number of participants: 30
Treatments
Experimental: Single Arm Treatment
Patients will receive pembrolizumab 200 mg intravenously (IV) on Day 1 of every 3-week dosing cycle (Q3W) and olaparib 300 mg capsules twice a day (BID) every day starting from Day 1 of Cycle 1. Treatment with protocol therapy will continue until objective disease progression, any prohibitive toxicity or until a maximum of 35 treatment cycles (up to 2 years).
Related Therapeutic Areas
Sponsors
Leads: Gruppo Oncologico del Nord-Ovest

This content was sourced from clinicaltrials.gov

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