Neoplasms

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Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

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Neoplasms, Squamous Cell

Head and Neck Neoplasms

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Amino Acids

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Serine

Threonine

AZD6738 (160 mg) tablet twice daily continuous dosing for a minimum of 9 days and a maximum of 21 days.

Olaparib (300 mg) tablets administered orally twice daily continuously for a minimum of 9 days and a maximum of 21 days.

Ceralasertib is an oral agent and will be dosed at 160 mg. Ceralasertib tablets should be taken at the same time each day, approximately 12 hours apart (maximum ± 2 hour window) with one glass of water.

Ceralasertib is a potent, selective inhibitor of the serine/threonine-specific protein kinase, ataxia telangiectasia and Rad3-related protein (ATR), with good selectivity against other phosphatidylinositol 3-kinase-related kinase (PIKK) family members.

Ceralasertib

Olaparib is available as a green film-coated tablet containing 100 mg or 150 mg of Olaparib. Patients will be administered Olaparib orally twice daily at 300 mg bid. The Olaprib tablets should be taken at the same time each day, approximately 12 hours apart with one glass of water.

Olaparib (AZD2281, KU-0059436) is a potent Polyadenosine 5'diphosphoribose \[poly (ADP ribose)\] polymerisation (PARP) inhibitor (PARP-1, -2 and -3) that is being developed as an oral therapy, both as a monotherapy (including maintenance) and for combination with chemotherapy and other anti-cancer agents.

Dr. Umamaheshwar Duvvuri

This biomarker study has been designed to assess the effects of different agents in both tumour tissue and peripheral samples to help inform the best combinations of DDR agents with immuno-oncology (IO) therapies. In the first instance 2 DDR agents will be assessed separately as monotherapy. Additional arms may be added later to evaluate other DDR agents and/or DDR and immunotherapy agents in combination or in sequence. The primary objective of the study is to investigate immune activation due to DDR inhibition by assessing tumour and blood samples of patients treated with study investigational agent(s).

Patients are dosed for a minimum of nine days with drug. Surgery or biopsy can then take place at any time between Day 10 and Day 21 (depending on when it can be scheduled), but must occur with 24 hrs following three consecutive treatment days. During the treatment period, safety assessments must be completed at least weekly.

Follow-up will be completed after surgical resection or biopsy has been completed and can be part of standard post-surgery follow-up. If this follow-up visit occurs prior to 30 days after the final dose, a further visit or telephone call must be conducted to assess that any toxicity has resolved and to check for late toxicity.

A Study to Investigate Biomarker Effects of Pre-Surgical Treatment With DNA Damage Repair (DDR) Agents in Patients With Head and Neck Squamous Cell Carcinoma (HNSCC).

A Clinical Trial to Investigate Biomarker Effects of Pre-Surgical Treatment With DDR Agents in Patients With Head and Neck Squamous Cell Carcinoma (HNSCC) Who Are Planned to Undergo Surgery That is Likely to be Followed by Radiotherapy and/or Chemotherapy.

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

To investigate prognosis-correlated immune activation due to DDR inhibition by monitoring the induction of immunologically relevant genes in tumours of patients treated with study investigational agent(s)

To investigate the prevalence and localization of TILs associated with prognosis.

To investigate the prevalence and localization of tumour infiltrating leukocytes (TILs) associated with prognosis.

Assessment of the safety for each DDR agent in terms of the incidences of the AEs

Assessment of the safety for each DDR agent in terms of the Vital signs

Assessment of the safety for each DDR agent in terms of the clinical chemistry / haematology assessments

Assessment of the safety for each DDR agent in terms of the ECG changes. A 12-lead ECG will be performed in triplicate at screening and at a time convenient during the visits (single ECG only required at subsequent visits).

Spots Global Cancer Trial Database for dna damage repair (ddr)