Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Antineoplastic Agents

Immunomodulating Agents

Durvalumab

Olaparib

Antineoplastic Agents, Immunological

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

PART 1: Pre-operative exposure of 160mg AZD6738 to be administered orally twice daily on Days 5 -14 of the WOP.

PART 2: 12 months post-operative exposure to 160mg AZD6738 to be administered orally twice daily on Days 1 - 14 of a 28 day cycle.

AZD6738

PART 1: Pre-operative exposure to 300mg of olaparib to be administered orally twice daily on Days 1-14 of the WOP.

PART 2: 12 months post-operative exposure to 300mg olaparib (2 x 150mg tablets) to be administered orally twice daily on a continuous schedule Day 1-28 of a 28 day cycle.

PART 1: Pre-operative exposure to 1500mg durvalumab to be administered via intravenous (IV) infusion on Day 1 only of the WOP.

PART 2: 12 months post-operative exposure to 1500mg durvalumab to be administered via intravenous (IV) infusion on Day 1 only of a 28 day cycle.

Hannah Johnson

Dr Castell

Dr Borley

Dr Irshad

Andrew Tutt

PHOENIX is a window of opportunity (WOP), open-label, multi-centre, phase IIa trial comprising multiple non-comparative treatment cohorts with patient allocation via randomisation. The trial consists of two parts: a post-neoadjuvant chemotherapy, preoperative WOP component (PART 1); and a post-operative component (PART 2).

PHOENX aims to assess whether short exposure to a DNA damage response (DDR) inhibitor and/or anti-PD-L1 immunotherapy in a preoperative WOP in patients with post-NACT high residual disease, generates a signal of anti-tumour biological activity within residual disease tissue.

Window of opportunity (WOP), open-label, multi-centre, phase IIa trial comprising multiple non-comparative treatment cohorts with patient allocation via randomisation.

The trial consists of two parts: a post-neoadjuvant chemotherapy preoperative WOP component (PART 1); and a post-operative component (PART 2).

PHOENIX DDR/Anti-PD-L1 Trial: A Pre-surgical Window of Opportunity and Post-surgical Adjuvant Biomarker Study of DNA Damage Response Inhibition and/or Anti-PD-L1 Immunotherapy in Patients With Neoadjuvant Chemotherapy Resistant Residual Triple Negative Breast Cancer

Change in mean proliferation index (as measured by tumour cell Ki67 immunohistochemistry) post WOP intervention within post-treatment biopsy compared to pre-treatment baseline biopsy. A patient will be defined as being a Ki67 responder if they experience a relative decrease in Ki67 positive cells of ≥33% in the surgical resection sample.

AND/OR Cohorts B and C co-primary endpoint #2, as described below.

Changes in the proliferation gene expression signature post WOP intervention within the post-treatment biopsy compared to pre-treatment baseline biopsy. A patient will be defined as being a responder if there is a ≥1.5-fold drop in the proliferation gene expression in the surgical resection sample.

The proliferation gene signature will be based on 11 highly correlated proliferation genes shown in multiple studies including those published by The Cancer Genome Atlas and they also contribute to the calculation of the proliferation score in the publicly available PAM50 classifier. The list consists of: CCNB1, UBE2C, BIRC5, NDC80, CDC20, PTTG1, RRM2, MKI67, TYMS, CEP55, and NUF2.

For each sample, a proliferation gene module score will be calculated according to the expression of the relevant genes.

AND/OR Cohorts B and C co-primary endpoint #1, as described above.

Change in CD8+ TILs post anti-PD-L1 immunotherapy within the post-treatment biopsy compared to pre-treatment baseline biopsy, assessed using immunohistochemistry. A patient will be defined as being a responder if they experience an increase in frequency of CD8+ counts by ≥2-fold within the surgical resection sample.

AND/OR Cohort D co-primary endpoint #2, as described below.

Changes in the interferon gamma-positive (IFNγ+) signature post WOP intervention within the post-treatment biopsy compared to pre-treatment baseline biopsy. A patient will be defined as being a responder if there is a ≥2-fold increase in the IFNγ+ gene expression in the surgical resection sample.The four-gene IFNγ+ score will be calculated, comprising of IFNγ, CD274, LAG3, and CXCL9.

AND/OR Cohort D co-primary endpoint #1, as described above.

Incidence of adverse events (AEs) during trial treatment (including surgical complications) by treatment cohort at 1 month post-surgery.

Changes in phosphorylation of ATR and its downstream effectors (Chk1, γH2AX, TAO upon drug exposure: including but not limited to levels of phosphorylation of p53, p38, p21/p27, cyclin dependent kinases (CDC25))

Changes in biomarkers of DDR and adaptive and innate response, including but not limited to 53BP1, RAD51, RPA, RPA32, pRPA, BRCA1/2, PARP expression and immune checkpoint ligands and receptors and adaptive and innate immune response markers (IFNg, cGAS-STING pathway, NKG2D receptors, ligands and cell markers) in the post treatment biopsy compared to pre-treatment baseline biopsy using gene expression profiling.

Assessment of associated expression of co-inhibitory immune checkpoint receptors using immune cell markers and high content image de-convolution.

Assessment of associated expression of co-inhibitory immune checkpoint ligands using immune cell markers and high content image de-convolution.

Assessment of frequency and function of tumour-infiltrating lymphocyte subsets using immune cell markers and high content image de-convolution.

Assessment of frequency and function of tumour-infiltrating myeloid cells subsets using immune cell markers and high content image de-convolution.

Change in the levels of Th1/IFNg response measured by transcriptional and proteomic profiling.

Immune cell population sub-set characterisation using appropriate and T and B cell receptor DNA sequencing methodologies.

AstraZeneca

Institute of Cancer Research, United Kingdom

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Lymphoma, Large B-Cell, Diffuse

Lymphoma

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Lymphosarcoma

Venetoclax

Obinutuzumab

Obinutuzumab is given in a 21 day cycle intravenously starting at 1000 mg on day 1, 8 and 15 in cycle 1 and on day 1 of each following cycle Venetoclax is given orally at a dose of 800mg daily from day 1 of the first cycle.

3 cycles followed by 9 cycles consolidation if not transplant eligible

Ulrich Jäger, MD

The purpose of this study is to evaluate the clinical activity and tolerability of a combination of obinutuzumab plus venetoclax in patients with relapsed or refractory diffuse large B-cell lymphoma.

The study will have a 6 patient run-in phase to determine safety and to adjust treatment. Once the sixth patient has completed 21 days of treatment, withdrawn due to toxicity, or died, a formal review will be undertaken by the sponsor (AGMT). Enrolment will be halted until review is completed. If one (1) treatment related death is reported or three (3) or more patients experience CTC grade 4 events other than neutropenia, anemia, or thrombocytopenia, the study will be stopped for further recruitment. If the stopping criteria are not met, enrollment will be continued. A futility analysis will be conducted when the first 10 patients have been evaluated for response: If at least 2 patients had an objective response (CR or PR), the study will be continued.

The combination treatment will be repeated for up to 3 cycles. The first response assessment (including PET-CT) will be performed after the first cycle of obinutuzumab-venetoclax and patients with at least stable disease (SD) or better will be given another 2 cycles of therapy and then have assessment after a total of 3 cycles. Patients with complete or partial remission (CR, PR) after 3 cycles of therapy will either go on to transplant or receive 9 further cycles of the combination therapy (if transplant ineligible). Patients with progressive disease at any time-point or stable disease after 3 cycles will be taken off study.

Combination of Obinutuzumab and Venetoclax in Relapsed or Refractory DLBCL

Phase II Single-arm "Window-of-opportunity" Study of a Combination of Obinutuzumab (GA-101) and Venetoclax (ABT-199) in Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)

Objective response rate (complete or partial responses; best response) defined by PET/CT scan and bone marrow examination examination after 3 cycles.

Incidence of dose-limiting toxicities of the combination treatment.

Assessed by number of eligible patients reaching transplant

Identification of genetically/biomarker defined subgroups regarding response and survival

Roche Pharma AG

Arbeitsgemeinschaft medikamentoese Tumortherapie

Amino Acids

Bevacizumab

Atezolizumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Ipatasertib

Angiogenesis Inhibitors

Growth Inhibitors

Immune Checkpoint Inhibitors

Protein Kinase Inhibitors

Serine

Threonine

Atezolizumab (1200mg IV D1 C1) + Cobimetinib (60mg PO D1 - 21 of C1)

Atezolizumab (1200mg IV D1 C1)+ Ipatasertib (400mg OD D1 - 21 of C1)

Atezolizumab (1200mg IV D1 C1)+ Cobimetinib (60mg PO D1 - 21 of C1) + Bevacizumab (10mg/kg IV D1 C1)

Highly selective small-molecule inhibitor of MEK1 and MEK2

Cobimetinib

Selective, ATP-competitive small molecule inhibitor of all three isoforms of the serine/threonine kinase Akt

Highly specific humanized monoclonal antibody that targets VEGF

Peter Schmid

International, open label, window of opportunity phase II trial that aims to evaluate the effects of immunotherapy based treatment combinations in women with untreated, histologically confirmed, operable, ER+, HER2-negative breast cancer.

ECLIPSE is an international, open label, window of opportunity phase II trial that aims to evaluate the effects of immunotherapy based treatment combinations in women with untreated, histologically confirmed, operable, ER+, HER2-negative breast cancer. The study is designed with the flexibility to open new treatment arms as new treatments become available, or modify the patient population e.g. with regards to biomarker status. Only combinations with adequate safety data will be tested. The trial will include Luminal B and non-Luminal B patients irrespective of PD-L1 status, but the number of patients with non-Luminal B tumours will be capped at 50% of the total study population. Luminal B tumours will be defined as high Ki67 (≥20%) and/or histological grade 3 or alternatively defined via PAM50 assay. All other types will be defined as non-Luminal B.

Eligible patients will be randomised with an approximately equal ratio (1:1:1:1) to one of four treatment arms (three experimental arms: (1) Atezolizumab + Cobimetinib, (2) Atezolizumab + Ipatasertib, (3) Atezolizumab + Cobimetinib + Bevacizumab and a control arm: Atezolizumab alone. Additional patients may be enrolled to ensure balance among treatment arms with respect to demographic and baseline characteristics, including potential predictive biomarkers, to enable further subgroup analysis. Thereafter, the randomisation ratio will depend on the number of experimental arms that are open for enrolment (e.g. if an arm is added or enrolment in an arm is suspended pending analysis of results. Randomisation will take into account arm-specific exclusion criteria and patients will be ineligible for a specific arm if they meet any of the exclusion criteria outlined for that arm.

Patients will receive treatment for 3 weeks prior to surgery or neoadjuvant therapy. Thereafter, patients will either be considered for definitive surgery or primary medical treatment (e.g. neoadjuvant chemotherapy) at the discretion of the treating physician. Surgery or neoadjuvant chemotherapy should be started within 3 weeks (±3 days) from the start of the study treatment. Patients will not be allowed to receive endocrine therapy prior to surgery.

Pre-operative Immunotherapy Combination Strategies in Breast Cancer

A Phase II Study Investigating Preoperative Combination Strategies for Immunotherapy in Patients With Untreated, Operable ER+, HER2-negative Primary Breast Cancer

Kliniken Essen-Mitte

MedSIR

Asan Medical Center

Hoffmann-La Roche

Queen Mary University of London

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Infections

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Uterine Cervical Neoplasms

Carcinoma, Squamous Cell

Virus Diseases

Oropharyngeal Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Patients with resectable stage I-III, HPV 16+ genotype squamous cell cancer of the oropharynx or unknown primary cancer site.

Patients with newly diagnosed HPV 16+ genotype advanced cervical cancer, clinical stages IB to IVB with plan for initial treatment of definitive chemoradiation.

HB-201 IV

HB-201 given IV, one (1) time, 7 to 14 days prior to definitive chemoradiation.

Chief Medical Officer

This Window of Opportunity clinical trial will examine the immunologic effects of the study agent HB-201 in the head and neck or cervical cancer, when administered by IV route.

The window of opportunity, Study H-200-002, will examine the effects of study agent (HB-201) on subjects during the "window" between diagnosis of their cancer and their definitive cancer surgery or chemoradiation.

The study will be a 2-arm study design. In Arm 1, the study will enroll subjects with resectable stage I-III human papillomavirus 16 positive (HPV 16+) genotype squamous cell cancer of the oropharynx or unknown primary cancer site who are candidates for transoral surgery. Participants will receive a single intravenous dose of the study agent HB-201 prior to transoral surgery administered intravenously.

In Arm 2, the study will enroll cervical cancer subjects who have histologically confirmed newly diagnosed advanced squamous cell carcinoma, adenocarcinoma, and/ or adenosquamous cell carcinoma with HPV 16+ genotype clincal stages IB to IVB with plan for initial treatment of definitive chemoradiation. Participants will receive a single intravenous dose of HB-201 prior to the start of chemoradiation.

A Study HB-201 in Patients With Newly Diagnosed HPV16+ Oropharynx or Locally Advanced Cervical Cancer

A Phase 0 Trial of HB-201 for Subjects With Transoral Resectable Human Papillomavirus 16 Positive (HPV 16+) Oropharynx Cancer or With Locally Advanced Cervical Cancer Treated With Chemotherapy and Radiation

Measurement of antigen-specific CD8+ T cells in blood and tissue (E7E6 antigen specific assay).

Number and type of adverse events per CTCAE v5.0

Hookipa Biotech GmbH

Heart and Blood Diseases

Heart Arrest

Cisplatin

Vinblastine

Tubulin Modulators

Antimitotic Agents

Part I: Patients will receive up to 3 doses of INT230-6 injected weekly prior to breast surgery

Part II: Patients will receive up to 2 intratumoral doses of INT230-6 (over a 15-day period) prior to breast surgery

Part I: No intervention while awaiting surgery

Part II: Placebo saline injection

INT230-6 is a formulation of two well known chemotherapeutic agents, cisplatin (0.5mg/mL) and vinblastine sulfate (0.1mg/mL), combined with 2-hydroxybenzoylaminooctanoate (also known as SHAO-FA or SHAO as a sodium salt at 10mg/mL).

INT230-6

Saline injection

Angel Arnaout, MD

Arif Awan, MD

This is a phase II, randomized, multi-center, parallel design, window of opportunity trial evaluating intratumoral INT230-6 in up to 90 patients with early stage breast cancer. In a 2:1 randomization, patients on the treatment arm will receive intratumoral INT230-6 injections prior to breast surgery.

The study comprises 2 consecutive parts. The first part will be to test safety and feasibility of the dosing procedures. Results from Part I of the study will standardise the optimal dose and frequency of INT230-6 for participants in Part II.

Part I: Open-label 2:1 randomized study of up to 30 patients. Treatment arm patients will be given up to 3 doses of INT230-6 injected weekly prior to breast surgery, at a dose based on longest diameter. The control arm patients receive no treatment.

Part II: Double-blind, 2:1 randomized study of up to an additional 60 patients. The placebo arm includes a saline injection of similar dose and frequency as the treatment arm (up to 2 doses of INT230-6/saline injected weekly prior to breast surgery).

INVINCIBLE TRIAL: Intratumoral INT230-6 in Breast Cancer

A Phase II Randomized Window of Opportunity Trial Evaluating Clinical and Biological Effects of Intratumoral INT230-6 in Early Stage Breast Cancer: The INVINCIBLE Trial

Tumor's viable plus necrotic tissue, at the post-treatment specimen.

Assessed by the local pathologist at the time of definitive surgery in subjects with breast cancer

Comparison of pre (diagnostic biopsy) and post treatment (surgical resection) samples

overall safety of INT230-6 injected prior to surgery

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
PHOENIX DDR/Anti-PD-L1 Trial: A Pre-surgical Window of Opportunity and Post-surgical Adjuvant Biomarker Study of DNA Damage Response Inhibition and/or Anti-PD-L1 Immunotherapy in Patients With Neoadjuvant Chemotherapy Resistant Residual Triple Negative Breast Cancer	NCT03740893	Breast Neoplasm	AZD6738 Olaparib Durvalumab	18 Years -	Institute of Cancer Research, United Kingdom
Combination of Obinutuzumab and Venetoclax in Relapsed or Refractory DLBCL	NCT02987400	Lymphoma, Large...	Venetoclax Obinutuzumab	18 Years -	Arbeitsgemeinschaft medikamentoese Tumortherapie
Pre-operative Immunotherapy Combination Strategies in Breast Cancer	NCT03395899	Breast Cancer Estrogen Recept...	Atezolizumab Cobimetinib Ipatasertib Bevacizumab	18 Years -	Queen Mary University of London
A Study HB-201 in Patients With Newly Diagnosed HPV16+ Oropharynx or Locally Advanced Cervical Cancer	NCT04630353	HPV 16+ Confirm...	HB-201 IV HB-201 IV	18 Years -	Hookipa Biotech GmbH
INVINCIBLE TRIAL: Intratumoral INT230-6 in Breast Cancer	NCT04781725	Breast Cancer	INT230-6 Saline injectio...	-	Ottawa Hospital Research Institute

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