A Phase III Randomized, Double Blind Placebo Controlled Study of BKM120 With Fulvestrant, in Postmenopausal Women With Hormone Receptor-positive HER2-negative Locally Advanced or Metastatic Breast Cancer Which Progressed on or After Aromatase Inhibitor Treatment
Patients were randomized (1:1) to receive buparlisib (100 mg/day) or placebo with fulvestrant
(500 mg); randomization was stratified by PI3K pathway activation status (activated,
non-activated, unknown determined in archival tumor tissue) and visceral disease status
(present or absent). Tumor evaluation was performed 6 weeks after the randomization date and
then every 8 weeks until radiological progression (based on Response Evaluation Criteria In
Solid Tumors [RECIST] version 1.1).
Novartis made the decision not to pursue further development of buparlisib and to terminate
the ongoing studies in the program. Accordingly, on 19-Dec-2016, Novartis notified all the
Investigators about the decision not to pursue further development of buparlisib in Breast
Cancer. As a result, the CBKM120F2302 study was terminated on 19-Apr-2019 (last subject last
visit).
An Open-Label, Multicenter, Phase 3 Study to Evaluate the Efficacy and Tolerability of Intravesical Vicinium™ in Subjects with Non Muscle-Invasive Carcinoma in Situ (CIS) and/or High-Grade Papillary Disease of the Bladder Previously Treated with Bacillus Calmette-Guérin (BCG).
Bladder cancer is the 6th most common cancer in the United States, affecting more men than
women. The usual first treatment for NMIBC (Ta, T1, and CIS) is transurethral resection of
the bladder tumors followed by intravesical immunotherapy, most commonly with bacillus
Calmette-Guérin (BCG).
Because of the high risk for development of muscle invasive disease, cystectomy is
recommended for CIS and high-grade Ta and T1 patients who experience disease recurrence
following intravesical therapy. For patients unable or unwilling to undergo cystectomy,
treatment options are limited.
Vicinium contains the active pharmaceutical ingredient VB4-845, which is a recombinant fusion
protein produced in Escherichia coli (E. coli) that expresses a humanized single-chain
antibody fragment specific for the epithelial cell adhesion molecule (EpCAM) antigen linked
to ETA(252-608). Once bound to the EpCAM antigen on the surface of carcinoma cells, Vicinium
is internalized through an endocytic pathway. The ETA(252-608) is cleaved off and induces
cell death by irreversibly blocking protein synthesis.
In vitro and in vivo pharmacology demonstrated that Vicinium exhibits potent activity
[inhibitory concentration 50% (IC50) = 0.001 - 10 pM] against numerous cell lines and
effectively inhibits tumor growth in several human xenograft animal models. A Phase 2 study
evaluated once-weekly instillations of Vicinium 30 mg over 6 or 12 weeks, followed by up to 3
maintenance cycles (3 once-weekly instillations followed by a 9-week drug-free period) in 45
subjects with histologically-confirmed TCC of the bladder and residual CIS with or without
concurrent Ta or T1 who were refractory or intolerant to BCG. A complete response (defined as
no histological evidence of disease and negative urine cytology at the 3-monthly evaluations)
was achieved by 44% of subjects, and 16% of subjects remained disease-free at 1-year. A
post-study assessment found that these subjects were still disease-free at 18-25 months. The
median time to recurrence was 134 days longer in subjects who received 12 weeks of induction
therapy compared to 6 weeks.
This is an open-label, non-randomized, multicenter study in adults with NMIBC, specifically
CIS (with or without papillary disease), high-grade Ta or any grade T1 papillary disease, who
have previously failed BCG treatment (i.e., not those who are intolerant) with or without
interferon. The study consists of a Screening period, a 12-week Induction Phase, and a
Maintenance Phase of up to 21 monthly cycles for a total treatment period of up to 104 weeks.
This is an outpatient study, but all treatments are administered in the study clinic.
Phase 2 Trial of Voyager V1 in Combination With Cemiplimab in Patients With Select Solid Tumors
Patients enrolled into three parallel doublet cohorts with an optimal Simon's two stage
design. Patients will receive Voyager V1 as a direct to tumor injection (IT) in all 3 cancer
groups and cemiplimab via IV infusion. Patients will return for treatment every 3 weeks until
lack of clinical benefit or limiting toxicity. Efficacy evaluations will be conducted every 6
weeks.
A Phase II Multicenter, Single Arm Study of Oral BGJ398 in Adult Patients With Advanced or Metastatic Cholangiocarcinoma With FGFR2 Gene Fusions or Other FGFR Genetic Alterations Who Failed or Are Intolerant to Platinum-based Chemotherapy
Adult patients with histologically or cytologically confirmed advanced or metastatic
cholangiocarcinoma with FGFR2 gene fusions or translocations or other FGFR genetic
alterations have been enrolled. Subjects must have received at least one prior regimen
containing gemcitabine with or without cisplatin for advanced/metastatic disease. Subjects
should have had evidence of progressive disease following their prior regimen or if prior
treatment was discontinued due to toxicity must have continued evidence of measurable
disease. Up to approximately 160 adult patients over age 18, both male and female were
planned for enrollment.
Three cohorts of subjects comprise the study population:
Cohort 1: subjects with FGFR2 gene fusions (ie, fusions or rearrangements [formerly
translocations]).
Cohort 2: subjects with FGFR genetic alterations other than FGFR2 gene fusions or
rearrangements.
Cohort 3: subjects with FGFR2 gene fusions or rearrangements who have received a prior FGFR
inhibitor.
All subjects received oral BGJ398 (infigratinib), once-daily, on a three weeks on (21 days),
one week off (7 days) schedule. One treatment cycle consists of 28 days.
Notes:
Cohort 1 was pre-specified as the primary analysis population. Results of these analyses were
previously disclosed (posted 22 June 2022). There were no additional efficacy or safety
endpoints to assess in Cohort 1 after primary completion (01 March 2021).
Cohorts 2 and 3 were added at protocol amendment (PA) 4 to support only exploratory efficacy
objectives of the study. These cohorts were ongoing the time of primary completion (01 March
2021). After interim review of the data from these cohorts (as permitted by the protocol)
only limited efficacy was observed and the sponsor terminated the study early. Therefore, a
formal efficacy analysis was not performed for Cohorts 2 and 3. However, baseline
characteristics and safety data were analyzed.
A Phase 1/2, Open-Label, Single-Arm, Dose-Escalation and Dose-Expansion Study of the Safety, Tolerability, Pharmacokinetic, and Antitumor Activity of E-602 as a Single Agent and in Combination With Cemiplimab in Patients With Advanced Cancers
This study is being conducted to evaluate the safety, tolerability, PK, pharmacodynamics, and
antitumor activity of E-602 in subjects with advanced cancers.
Phase 1 of the study consists of dose escalation cohorts of E-602 as a monotherapy and in
combination with cemiplimab. Dose escalation will utilize a modified 3+3 design. Any Phase 1
cohort may be backfilled, up to a total of 15 subjects to obtain additional safety, PK, and
pharmacodynamic data at a particular dose level. Phase 1 will treat subjects with melanoma,
ovarian cancer, non-small cell lung cancer (NSCLC), colorectal cancer, pancreatic cancer,
breast cancer, gastric/esophagogastric junction (EGJ) cancer, head and neck cancer, or
urothelial cancer. The safety and pharmacodynamic data will be evaluated to identify the
maximum tolerated dose and recommended Phase 2 dose level for E-602 as monotherapy and in
combination with cemiplimab.
Phase 2 consists of dose-expansion disease cohorts in subjects with 3 types of advanced
tumors: melanoma, NSCLC, and a third type to be determined (ovarian, colorectal, pancreatic,
breast, gastric/EGJ, head and neck, or urothelial) based on available data. Phase 2 includes
cohorts of E-602 as monotherapy and E-602 in combination with camiplimab. For each cohort in
Phase 2, Simon's minimax 2-stage design will be used.
The study is seeking to enroll a total of up to 273 subjects (up to 87 in Phase 1 and up to
186 in Phase 2). Subjects will participate in the study for about 16 months.
A Phase 1a/1b Dose Escalation/Expansion Study of TTX-080, an HLA-G Antagonist, as Monotherapy and in Combination With Pembrolizumab or Cetuximab in Patients With Advanced Solid Refractory/Resistant Malignancies
TTX-080 is a fully human mAb designed to block the interaction of HLA-G with its known
ligands, ILT2 and ILT4 molecules. The Phase 1a was an open label, multicenter, dose
escalation clinical trial to determine the safety, tolerability, MTD or OBD and the RP2D of
TTX-080 when administered as a single agent. The Phase 1b is a dose expansion of TTX-080
monotherapy and in combination with either pembrolizumab or cetuximab in adult subjects with
advanced refractory/resistant solid malignancies, including Head and Neck squamous cell
carcinoma (HNSCC), Non-Small Cell Lung Cancer (NSCLC), Colorectal cancer (CRC), triple
negative breast cancer (TNBC), renal cell carcinoma (RCC), and acral melanoma. Additionally,
the study will seek to evaluate the pharmacokinetics and immunogenicity of TTX-080, and
preliminary efficacy of TTX-080 as a monotherapy and in combination with pembrolizumab or
cetuximab.
Phase 1 / 2 Multicenter Study of the Safety, Pharmacokinetics, and Preliminary Efficacy of APL-101 in Subjects With Non-Small Cell Lung Cancer With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors
Phase 1 (lead-in stage of this study) enrollment has been completed.
In this Phase 2 study, efficacy, safety, and tolerability will be assessed in the following
cohorts:
- Cohort A-1: NSCLC EXON 14 skip mutation, previously untreated, MET inhibitor naive
(c-Met naïve, 1L)
- Cohort A-2: NSCLC EXON 14 skip mutation, previously treated with ≤ 3 prior lines in
unresectable or metastatic setting, MET inhibitor naive (c-Met naïve, 2/3L)
- Cohort B: NSCLC EXON 14 skip mutation, previously treated with ≤ 3 prior lines in
unresectable or metastatic setting, MET inhibitor experienced (c-Met experienced;
progressed on prior c-Met inhibitor)
- Cohort C: basket of tumor types (e.g., NSCLC, upper gastrointestinal [GI], colorectal,
hepatobiliary cancer) harboring MET amplification except for primary CNS tumors,
previously treated or previously untreated but refused standard treatment, or if
treatment was unavailable or unfeasible (≤ 3 prior lines in unresectable or metastatic
setting), MET inhibitor naïve
- Cohort C-1: NSCLC harboring MET amplification and wild-type epidermal growth factor
receptor (EGFR), previously treated; or untreated but refused standard treatment, or if
treatment was unavailable or unfeasible (≤ 3 prior lines in unresectable or metastatic
setting), MET inhibitor naïve
- Cohort C-2: EGFR positive NSCLC harboring MET amplification as an acquired resistance,
documented response with first-line EGFR-Inhibitor (PR or CR per RECIST ≥ 12 weeks),
radiological documentation of disease progression per RECIST on first-line EGFR
inhibitor therapy, MET inhibitor naïve
- Cohort D: basket of tumor types except for primary CNS tumors harboring MET gene fusions
(e.g., NSCLC, upper GI, colorectal, hepatobiliary cancer), previously treated; or
previously untreated but refused standard treatment, or if treatment was unavailable or
unfeasible (≤ 3 prior lines in unresectable or metastatic setting), MET inhibitor naïve
- Cohort E: primary CNS tumors with MET alterations (single or co-occurred MET fusion
including PTPRZ1-MET [ZM] fusion, MET Exon 14 skipping mutation, or MET amplification),
previously treated or previously untreated but refused standard treatment, or if
treatment was unavailable or unfeasible (≤ 3 prior lines), MET inhibitor naïve
- Cohort F: basket of tumor types harboring wild-type MET with over-expression of HGF and
MET (e.g., NSCLC, upper GI, colorectal, hepatobiliary cancer or primary CNS tumors),
previously treated; or previously untreated but refused standard treatment, or if
treatment was unavailable or unfeasible (≤ 3 prior lines in unresectable or metastatic
setting), MET inhibitor naïve
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