A Phase 1, Multicenter, Single Agent Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of CPO301, an EGFR-Targeting Antibody-Drug Conjugate, in Adult Patients With Advanced or Metastatic Solid Tumors
This Phase 1 study is a multicenter, dose-escalating, dose-expansion, single agent, 2-part
study conducted in patients with advanced or metastatic solid tumors who progressed on ≥1
prior conventional systemic therapy or who were ineligible or intolerant to standard
treatment or had no or refused standard treatment.
Dose escalation (Part A) - Dose escalation will be guided by a modified 3+3 design to
determine the maximum tolerated dose (MTD) or recommended dose of CPO301 (also known as
SYS6010). Determination of dose-limiting toxicity (DLT) will be based on toxicity observed
during the DLT observation period (first 21 days [1 cycle]). Dose escalation decisions are
made based on the occurrence of DLT. MTD will be determined based on the data of all enrolled
participants. To better identify the MTD, one or more dose groups may also be added beyond
the planned maximum dose group (if determined to be safe), or between the maximum escalation
dose group and the next lower dose group for DLT assessment. Intermediate dose groups and/or
adjustment to the dosing frequency may be made
Dose expansion (Part B) - Additional patients will be enrolled at the recommended dose
determined in the dose escalation stage. An additional tumor cohort may be added based on
data observed in Part A.
Short-Term Fasting Prior to Standard Checkpoint Blockade Using PD-1/PD-L1 Inhibition: A Pilot Safety and Feasibility Study
PRIMARY OBJECTIVES:
I. To evaluate the safety and feasibility of short term fasting in combination with PD-1
inhibition therapy for patients with advanced malignancy.
Ia. To estimate the percentage of patients who adhere completely to short term fasting (STF)
in combination with PD-1 inhibition therapy for 3 cycles.
Ib. To estimate the percentage of patients who develop unacceptable fasting-related toxicity.
SECONDARY OBJECTIVES:
I. To measure how many patients can adhere with STF for at least 2 cycles in combination with
PD-1 inhibition.
Ia. To estimate the percentage of patients who adhere to STF in combination with PD-1
inhibition therapy for at least 2 cycles, or a total of at least 6 out of 9 days.
II. To measure all grades of fasting-related toxicity. IIa. To estimate the percentage of
patients who develop any grades of fasting-related toxicity, including acceptable
fasting-related toxicity.
EXPLORATORY OBJECTIVES:
I. The efficacy of combining STF with PD-1/PD-L1 inhibition will be assessed by Response
Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 response rate, as measured at
the time of tumor assessment after 3 cycles of treatment.
II. The immune-related toxicity of combining STF with PD-1/PD-L1 inhibition will be recorded
at the start of each cycle, and graded per Common Terminology Criteria for Adverse Events
(CTCAE) v 4.0.
III. Quality of life during STF combined with PD-1/PD-L1 inhibition will be recorded using
the Functional Assessment of Cancer Therapy - General (FACT-G) version 4, questionnaire tool.
IV. Fasting-related biomarkers to measure the impact of STF during PD-1/PD-L1 inhibition
include measurement of serum insulin/IGF-1, PI3K/AKT/mTOR signaling, MAPK pathway signaling,
and markers of oxidative stress.
V. Immune biomarkers will be analyzed using immunohistochemistry and ribonucleic acid (RNA)
expression studies.
OUTLINE:
Patients undergo STF for 47-48 hours prior to immunotherapy and for 24 hours after
immunotherapy with standard of care pembrolizumab given intravenously (IV) over 30 minutes,
nivolumab IV over 30 minutes, cemiplimab IV over 30 minutes, avelumab IV over 60 minutes,
atezolizumab IV over 60 minutes, or durvalumab IV over 60 minutes on day 3. Treatment repeats
every 21 days for up to 3 cycles in the absence of disease progression or unacceptable
toxicity.
After completion of study treatment, patients are followed up in 3-6 weeks.
Phase III Trial of Immunotherapy-Based Combination Therapy With or Without Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma (PROBE Trial)
PRIMARY OBJECTIVE:
I. To compare overall survival in participants with newly diagnosed metastatic renal cell
carcinoma who are randomized to receive immune checkpoint inhibitor-based combination
treatment plus cytoreductive nephrectomy versus immune checkpoint inhibitor-based combination
treatment alone.
SECONDARY OBJECTIVES:
I. To compare overall survival between arms in the subset who received their assigned
protocol treatment.
II. To assess complications of nephrectomy and post-randomization drug toxicities.
III. To compare objective response rate in metastatic sites between the arms in participants
with measurable metastatic disease.
IV. To assess change in diameter of primary tumor at week 12 disease assessment in
participants who have received pre-randomization treatment.
BANKING OBJECTIVE:
I. To bank specimens for future correlative studies.
OUTLINE:
PRE-RANDOMIZATION TREATMENT: Treatment naive patients are assigned to 1 of 3 treatment
regimens per standard of care.
REGIMEN I: Patients receive nivolumab intravenously (IV) and ipilimumab IV. Treatment repeats
every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable
toxicity. Patients then receive nivolumab IV on day 1. Cycles repeat every 2-4 weeks in the
absence of disease progression or unacceptable toxicity.
REGIMEN II: Patients receive pembrolizumab IV on day 1 and axitinib orally (PO) twice daily
(BID) on days 1-21. Cycles repeat every 3 weeks in the absence of disease progression or
unacceptable toxicity.
REGIMEN III: Patients receive avelumab IV on day 1 and axitinib PO BID on days 1-14. Cycles
repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.
NOTE: Some patients may have already completed the standard of care pre-randomization
treatment specified above off-trial.
RANDOMIZATION TREATMENT: Between 10-14 weeks from the start of on-trial or off-trial
pre-randomization treatment, patients are randomized to 1 of 2 arms.
ARM I: Patients receive nivolumab IV, pembrolizumab IV, or avelumab IV on day 1. Patients
also receive axitinib PO BID. Cycles with nivolumab repeat every 2 or 4 weeks, cycles with
pembrolizumab repeat every 3 weeks, and cycles with avelumab repeat every 2 weeks in the
absence of disease progression or unacceptable toxicity.
ARM II: Within 42 days following randomization, patients undergo radical or partial
nephrectomy in addition to nivolumab, pembrolizumab, avelumab, and axitinib as in Arm I in
the absence of disease progression or unacceptable toxicity. Axitinib should be stopped at
least 24 hours prior to surgery.
After completion of trial treatment, patients are followed up every 3 months for the first
year, every 6 months for years 2 and 3, and then annually for up to 7 years from
randomization.
A Phase II, Open-Label, Multi-Cohort, Multicenter Study in Patients With Unresectable Hepatocellular Carcinoma and Child-Pugh B7 and B8 Cirrhosis
This is a Phase II, open-label, multicohort, multicenter study in participants with
unresectable, locally advanced, or metastatic hepatocellular carcinoma (HCC) who have
Child-Pugh B7 or B8 liver cirrhosis and have received no prior systemic therapy in this
treatment setting. The study is designed to non-comparatively evaluate the safety and
efficacy of atezolizumab plus bevacizumab (Cohort A) or atezolizumab monotherapy (Cohort B)
in this population.
The HistoSonics Edison System for Treatment of Primary Solid Renal Tumors Using Histotripsy (#HOPE4KIDNEY US)
This trial is a prospective, multi-center, single-arm pivotal trial designed to evaluate the
effectiveness and safety of the HistoSonics Edison System for the destruction of kidney
tissue by treating primary solid renal tumors. Data through 90 days for all enrolled subjects
will be summarized in a primary analysis to be submitted for Regulatory Submission to the
FDA. Additionally, subjects will be followed for five (5) years post-index procedure, with
evaluations at the 14-day, 30-day, 90-day, 180-day and annual time points.
A Phase I/II Study of TheraT® Vector(s) Expressing Human Papillomavirus 16 Positive (HPV 16+) Specific Antigens in Patients With HPV 16+ Confirmed Cancers
HB-201 and HB-202 are study drugs which are designed to train the body to recognize and fight
substances found in HPV 16+ cancer. This trial studies the safety and anti-cancer effect of
HB-201 and HB-202 in people.
The trial is enrolling patients with metastatic/recurrent head and neck cancer who have not
yet received treatment in this setting (1L, first line) and who are eligible to receive
pembrolizumab as part of their standard of care. This trial is also enrolling patients with
metastatic/recurrent head and neck who have received prior treatment in this setting (2L+,
second and later line) who are eligible to receive pembrolizumab as part of their standard of
care. Patients will receive the study drugs in addition to their pembrolizumab standard of
care regimen.
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