An Open-label, Multicenter, Phase 1a/1b Study of Aplitibart (IGM-8444) as a Single Agent and in Combination in Participants With Relapsed, Refractory, or Newly Diagnosed Cancers
Participants will be enrolled in Phase 1a, which consists of two stages: a dose-escalation
stage and an expansion stage. Aplitabart will be used as a single agent and in combination
with numerous other agents where standard therapeutic regimens do not exist, have proven to
be ineffective or intolerable, or are considered inappropriate.
Colorectal participants may be enrolled in Phase 1b, an open-label, randomized study of
aplitabart+FOLFIRI+ bevacizumab.
Aplitabart will be investigated in numerous tumor types including all-comers solid tumors,
colorectal carcinoma (CRC), sarcoma, non-Hodgkin's lymphoma (NHL), acute myeloid leukemia
(AML), and chronic lymphocytic leukemia (CLL).
Aplitabart will be administered intravenously (IV).
An alternative dosing schedule may be evaluated.
A Modular Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Ceralasertib in Combination With Cytotoxic Chemotherapy and/or DNA Damage Repair/Novel Anti-cancer Agents in Patients With Advanced Solid Malignancies.
This is a modular, phase I, two part, open-label, multicentre study of ceralasertib,
administered orally, in combination with cytotoxic chemotherapy regimens and/or novel
anti-cancer agents, to patients with advanced/metastatic solid malignancies. The study design
allows an escalation of the dose of ceralasertib in combination with the standard dose and
schedule of either cytotoxic chemotherapies and/or novel anti-cancer agents, with intensive
safety monitoring to ensure the safety of the patients. There are two parts to each
combination module of this study; part A, dose escalation and an optional part B, cohort
expansions in particular patient groups. The initial combination module will be with
Carboplatin (module 1). The second combination will be with Olaparib (module 2). The third
combination will be with durvalumab (module 3), the fourth combination will be AZD5305
(Module 5). The option to start further combination modules will be the decision of the
Safety Review Committee (SRC), based on emerging preclinical data and, safety and
tolerability information from the initial combination. Combinations of ceralasertib with
novel anti-cancer agents may also be explored. Once a minimally biologically active dose of
ceralasertib, for that combination module, has been identified from part A of that module,
the SRC may decide to commence part B if deemed to be necessary. This may include cohort
expansions of specific patient groups to explore preliminary anti-tumour activity or the
effect of food or particular drug combinations on drug pharmacokinetics. The fourth module
will investigate the effect of food on ceralasertib absorption and whether ceralasertib has
an effect on QT.
A Window of Opportunity Study of Taxanes in Head and Neck Cancer
PRIMARY OBJECTIVE:
I. To describe the phenotypical and functional changes of different T cell subsets within the
tumor microenvironment after treatment with FID-007.
SECONDARY OBJECTIVES:
I. To describe the adverse events associated with neoadjuvant FID-007 prior to surgery for
head and neck cancer.
II. To evaluate preliminary evidence of efficacy by describing the rate of major and complete
pathologic response.
III. To describe the rates of locoregional recurrence and rate of distant metastasis at 2
years after surgery.
EXPLORATORY OBJECTIVE:
I. Explore association between pathologic response and phenotypical and functional changes in
T cell subsets.
OUTLINE:
Patients receive FID-007 intravenously (IV) over 30 minutes once a week for 3 weeks on days
1, 8, and 15 of a single 28 day cycle in the absence of disease progression or unacceptable
toxicity. Patients then undergo standard of care surgery. Patients undergo computed
tomography (CT) or magnetic resonance imaging (MRI) during screening and blood sample
collection throughout the study.
After completion of study treatment, patients are followed up every 3 months for 2 years.
A Phase II Open Label, Single Arm Study to Evaluate the Efficacy of Pembrolizumab for Leukoplakia
PRIMARY OBJECTIVES:
I. Clinical response rate at 6 months? percent of patients with complete response and partial
response at 6 months.
SECONDARY OBJECTIVES:
I. Histologic response rate at 6 months. II. Change in clinical impression based on
photographs of the lesion. III. Clinical response rate at 9 months and 12 months. IV.
Toxicity.
EXPLORATORY OBJECTIVES:
I. PD-L1 expression in leukoplakia lesions and biomarker analysis.
OUTLINE:
Participants receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses
repeat every 3 weeks for 6 months in the absence of disease progression or unacceptable
toxicity.
After completion of study treatment, participants are followed up at 30 days and every 3
months for 2 years.
A Phase 2a, Randomized, Open-Label Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS 702843 Administered to Patients With Phlebotomy Dependent Polycythemia Vera (PD-PV)
This is a Phase 2a, multi-center, randomized, open-label study of sapablursen in up to 40
participants with PD-PV. The study consists of 4 periods: 1) Screening Period: up to 7 weeks;
2) Treatment Period: 37 weeks 3) Treatment Extension Period: 36 weeks; 4) Post-treatment
Period: 13 weeks.
In the Treatment Period, study drug is given by subcutaneous (under the skin) injection(s).
There will be a total of 9 doses given over about 8 months.
In the Treatment Extension Period, there will be a total of 9 doses given over about 8
months.
Participants will be assigned to receive one of 2 Dosing Levels - a higher or a lower level,
with an equal chance of being assigned to either Dosing Level. All participants will receive
study drug; there is no placebo.
This study was extended to allow participants to receive sapablursen for an additional 36
weeks following the initial 37-week treatment period.
A Phase 1 Open-label, Multicenter, Dose-ranging Study to Investigate Safety and Tolerability, Efficacy, Pharmacokinetics, Pharmacodynamics and Immunogenicity of MT-6402 in Subjects With Advanced Solid Cancer That Expresses PD-L1
This study will be conducted in two sequential parts:
- Part 1 (Dose Escalation): The purpose of Part 1 is to evaluate the safety and
tolerability of MT-6402 in subjects with advanced cancer (solid tumors) and to estimate
the maximum tolerated dose (MTD)
- Part 2 (Dose Expansion): The purpose of Part 2 is to confirm the recommended Phase 2
dose (RP2D) and to evaluate the efficacy of MT-6402 in subjects with advanced cancer.
Part 2 will include subjects with PD-L1 positive non-small cell lung cancer (NSCLC) who
received prior PD-1/PD-L1 treatment, subjects with PD-L1 positive squamous cell cancer
of the head and neck (SCCHN) who are refractory to or ineligible for platinum-based
therapy and received prior PD-1/PD-L1 treatment and subjects with any other relapsed or
refractory PD-L1 positive solid tumor who received PD-1/PD-L1 treatment.
Up to 138 eligible subjects will be identified and treated through competitive enrollment at
multiple study centers
In Parts 1 and 2, a subject may participate for the following four (4) periods:
- Screening Period - up to 28 days before first dose of MT-6402
- Treatment Period - active period where a subject will receive doses of MT-6402 over a
28-day treatment period
- Short-term Follow-up Period - up to 90 days after last dose of MT-6402
- Long-term follow-up Period - up to 24 months after last dose of MT-6402
MT-6402 will be given as an intravenous (IV) infusion over 30 minutes on the same day every
week (i.e., days 1, 8, 15 and 22) of each cycle. A cycle is defined as 28 days. A subject can
continue receiving MT-6402 as long as it is well-tolerated or until the subject decides they
no longer want to participate in the study.
Phase 1 Study of Erdafitinib Intravesical Delivery System (TAR-210) in Participants With Non- Muscle-Invasive or Muscle-Invasive Bladder Cancer and Selected FGFR Mutations or Fusions
Bladder cancer is one of the most common malignancy worldwide, and non-muscle invasive
(NMIBC) requires intensive regimens of frequent monitoring and local resection (transurethral
resection of bladder [TURBT]). This study enrolls participants with non-muscle invasive or
muscle invasive bladder cancer with activating fibroblast growth factor receptor (FGFR)
mutations or fusions. Erdafitinib is a pan-FGFR inhibitor with demonstrated clinical activity
when administered orally in patients with solid tumors, including bladder cancer, with FGFR
genetic alterations. The Erdafitinib intravesical delivery system is designed to provide
release of Erdafitinib in the bladder to treat localized bladder cancer, while reducing
systemic toxicities. The study consists of a screening phase, a treatment phase, and a
follow-up phase. Total duration of the study is 5 years 3 months.
A Randomized Phase III Trial of Intravesical BCG veRsus Intravesical Docetaxel and GEmcitabine Treatment in BCG Naïve High Grade Non-Muscle Invasive Bladder Cancer (BRIDGE)
The primary objective of this study is to determine the event free survival (EFS) of
BCG-naïve high grade non-muscle invasive bladder cancer patients treated with intravesical
BCG vs Gemcitabine + Docetaxel. Secondary objectives are as follows: to compare changes in
cancer-specific and bladder cancer-specific QOL from baseline to treatment between BCG-naïve
high grade NMIBC patients receiving BCG and GEMDOCE, to determine the cystectomy free
survival (CFS) of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs
GEMDOCE, to determine the progression free survival (PFS) of BCG-naïve high grade NMIBC
patients treated with intravesical BCG vs GEMDOCE, and to determine the safety and toxicity
of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs GEMDOCE
A Phase 1a, Dose Escalation, Safety and Tolerability Study of NX-1607, a Casitas B-lineage Lymphoma Proto-oncogene (CBL-B) Inhibitor, in Adults With Advanced Malignancies, With Phase 1b Expansion in Select Tumor Types
Phase 1a will consist of 2 study arms: Monotherapy and Paclitaxel combo. Phase 1a dose
escalation will evaluate the safety and tolerability of NX-1607 in adult patients with
advanced solid tumors for which standard therapy with proven clinical benefit does not exist,
is no longer effective, or is not appropriate. Indications for monotherapy include platinum
resistant epithelial ovarian cancer (EOC), gastric/gastroesophageal junction (GEJ) cancer,
squamous cell carcinoma of the head and neck (HNSCC), recurrent and either metastatic or
unresectable melanoma, non-small cell lung cancer (NSCLC), metastatic castration-resistant
prostate cancer (mCRPC), malignant pleural mesothelioma (MPM), triple-negative breast cancer
(TNBC), locally advanced or metastatic urothelial cancer, cervical cancer, and microsatellite
stable colorectal cancer (MSS CRC), and diffuse large cell B-cell lymphoma (DLBCL) including
patients with Richter transformation (DLBCL-RT). Indications for paclitaxel combo may
include, but are not limited to, platinum-resistant EOC, gastric/GEJ cancer, HNSCC, NSCLC,
TNBC, locally advanced or metastatic urothelial cancer, and cervical cancer at the Sponsor's
discretion.
Phase 1b will investigate the efficacy of NX-1607 as monotherapy or in combination with
paclitaxel at the dose(s) selected in Phase 1a in up to 8 cohorts of patients with select
advanced malignancies for which standard therapy, including immunotherapy, with proven
clinical benefit does not exist, is no longer effective, or is not appropriate. Indications
include platinum-resistant EOC, including primary peritoneal and fallopian tube carcinoma,
advanced gastric/GEJ cancer, HNSCC, recurrent and either metastatic or unresectable melanoma,
advanced NSCLC, mCRPC, mixed solid tumor cohort indications consisting of patients with MPM,
TNBC, locally advanced or metastatic urothelial cancer, cervical cancer, or MSS CRC, and
DLBCL including patients with DLBCL-RT.
A Phase 1/2 Study of the Bromodomain Inhibitor ZEN003694 in Combination With Etoposide/Platinum in Patients With NUT Carcinoma
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the
addition of BET bromodomain inhibitor ZEN-3694 (ZEN003694) to etoposide and cisplatin (EP) in
participants with NUT Carcinoma (NC). (Phase 1) II. Evaluate the overall objective response
rate (ORR) of the addition of ZEN003694 to etoposide and cisplatin (EP) in participants with
NC utilizing response evaluation criteria in solid tumors (RECIST) version 1.1 criteria
(Phase 2)
SECONDARY OBJECTIVES:
I. Evaluate the preliminary progression-free survival (PFS) rate, ORR, duration of response
(DoR), and overall survival (OS) of the addition of ZEN003694 to etoposide and cisplatin (EP)
in participants with NC utilizing RECIST version 1.1 criteria. (Phase 1) II. Determine the
pharmacokinetic (PK) profile of ZEN003694, etoposide, and cisplatin when administered in
combination. (Phase 1) III. Further evaluate PFS, DoR, and OS of ZEN003694, etoposide, and
cisplatin in participants with NC using RECIST version 1.1 criteria (Phase 2) IV. Confirm the
safety and tolerability of the regimen in this patient population. (Phase 2) V. Confirm the
recommended phase 2 dose (RP2D) from the Phase 1 portion of the trial by assessing the
totality of the evidence (i.e., safety, tolerability, pharmacokinetic, pharmacodynamic and
activity data) from this trial to select optimal doses for future trials with registrational
intent. (Phase 2) VI. Evaluate the preliminary ORR, PFS DoR, and OS of ZEN003694 monotherapy
in a small exploratory cohort of patients with non-thoracic origin, non-BRD4-NUT NC. (Phase
2) VII. To observe and record anti-tumor activity. (Phase 1, phase 2, non-thoracic, non-BRD4
exploratory cohort) VIII. Explore potential biomarker indicators of response and resistance
in tumor tissue samples. (Phase 1, phase 2, non-thoracic, non-BRD4 exploratory cohort)
IX. To perform molecular profiling assays on malignant and normal tissues, including, but not
limited to, whole exome sequencing (WES) and messenger ribonucleic acid (RNA) sequencing
(RNAseq), in order to:
IXa. Identify potential predictive and prognostic biomarkers beyond any genomic alteration by
which treatment may be assigned; (Phase 1, phase 2, non-thoracic, non-BRD4 exploratory
cohort) IXb. Identify resistance mechanisms using genomic deoxyribonucleic acid (DNA)- and
RNA-based assessment platforms. (Phase 1, phase 2, non-thoracic, non-BRD4 exploratory cohort)
X. To contribute genetic analysis data from de-identified biospecimens to Genomic Data
Commons (GDC), a well annotated cancer molecular and clinical data repository, for current
and future research; specimens will be annotated with key clinical data, including
presentation, diagnosis, staging, summary treatment, and if possible, outcome. (Phase 1,
phase 2, non-thoracic, non-BRD4 exploratory cohort) XI. To bank formalin-fixed,
paraffin-embedded (FFPE) tissue, blood (for cell-free DNA analysis), and nucleic acids
obtained from patients at the National Cancer Institute (NCI) Early-Phase and Experimental
Clinical Trials Biospecimen Bank (EET Biobank) at Nationwide Children's Hospital. (Phase 1,
phase 2, non-thoracic, non-BRD4 exploratory cohort)
OUTLINE: This is a phase I dose escalation study of ZEN003694 with fixed dose etoposide and
cisplatin followed by a phase 2 study.
Patients receive ZEN003694 orally (PO) once or twice daily on days 1-14 or days 1-21 of each
cycle depending upon dosage assignment. Patients also receive etoposide intravenously (IV)
over 60 minutes on days 1-3 for cycles 1-4 or up to 8 cycles, and cisplatin IV over 60
minutes on day 1 of cycles 1-4 or up to 8 cycles. Cycles repeat every 21 days in the absence
of disease progression or unacceptable toxicity. Patients may undergo radiologic evaluation
(chest x-ray, computed tomography [CT], positron emission tomography [PET]-CT, magnetic
resonance imaging [MRI], and/or fludeoxyglucose [FDG]-PET) at the completion of every 2
cycles or 6 weeks, and then at the end of every 3 or 4 cycles after the completion of cycle
10. Patients may also undergo biopsy between cycle 1 day 4 and cycle 1 day 14.
After completion of study treatment, patients are followed for 30 days after the last dose
and then every 4 weeks for a maximum of 2 years.
Core Biopsies of Breast Tumor Tissue Repository
PRIMARY OBJECTIVES:
I. To develop a baseline and serial breast cancer core biopsy repository within the
University of Southern California (USC)/Norris Comprehensive Cancer Center Women's Cancer
Program.
II. To develop and maintain a secure clinical database of relevant demographic, clinical,
pathologic and longitudinal outcome characteristics of the samples to be banked.
III. To have an efficient process for the distribution of de-identified samples from the bank
to researchers with institutional review board (IRB)-approved protocols or exemptions for the
study of breast cancer-related questions. These studies would include analyses of tumor
proteins and nucleic acids, serum/plasma and germline deoxyribonucleic acid (DNA) and immune
cells in relationship to other baseline and follow-up clinical and pathological variables.
OUTLINE: Patients are assigned to 1 of 4 cohorts.
COHORT I (PATIENTS WITH NEWLY DIAGNOSED EARLY STAGE BREAST CANCER WHO WILL UNDERGO DEFINITIVE
SURGERY BEFORE ANY SYSTEMIC THERAPY): Patients undergo baseline and, if applicable, follow-up
core needle biopsies of breast cancer in the breast, regional nodes, and distant metastases.
Patients who experience a recurrence or progression after therapy undergo additional core
biopsies at the time of recurrence. Clinical and blood specimens will also be gathered.
COHORT II (PATIENTS WITH NEWLY DIAGNOSED BREAST CANCER WHO WILL RECEIVE STANDARD OF CARE
SYSTEMIC THERAPY BEFORE SURGERY OR PATIENTS WITH ADVANCED UNRESECTABLE DISEASE): Patients
undergo core biopsy, clinical, and blood sample collection as in Cohort I. Patients also
undergo biopsies at a specific time point following the initiation of standard systemic
therapy.
COHORT III (PATIENTS BEING EVALUATED FOR A SUSPICIOUS BREAST MASS THAT HAS A HIGH LIKELIHOOD
OF BEING CANCER): Patients undergo core biopsy, clinical, and blood sample collection as in
Cohort I. Patients who have Breast Imaging-Reporting and Data System (BIRADS) 4b, 4c, and 5
lesions may undergo up to 6 additional 6 core biopsies.
COHORT IV (PATIENTS WITH BREAST CANCER RECURRENCE OR PROGRESSION [LOCAL, REGIONAL, OR
DISTANT/METASTATIC]): Patients undergo core biopsy, clinical, and blood sample collection as
in Cohort I. Patients may also undergo 1-3 extra core biopsies.
After completion of study, patients are followed up every 6 months.
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