A Multi-Center, Open-Label Phase 1b/2 Study of a Novel FGFR3 Inhibitor (B-701) Combined with Pembrolizumab in Subjects with Locally Advanced or Metastatic Urothelial Carcinoma who have Progressed Following Platinum-based Chemotherapy or are not eligible for cisplatin-containing chemotherapy.

Withdrawn

• Conditions: Bladder cancer; Transitional cell carcinoma; 10038364

• Registration Number: NL-OMON48991
• Lead Sponsor: Rainier Therapeutics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 23 April 2024

Recruitment & Eligibility

• Status: Withdrawn
• Sex: Not specified
• Target Recruitment: 2

Inclusion Criteria

1. Have locally advanced (on TNM staging: T4b and any N, or any T and N2-3) or
metastatic transitional cell carcinoma of the urothelium, including the urinary
bladder, urethra, ureter, and/or renal pelvis. The diagnosis must be
histologically or cytologically confirmed.
For subjects in the Phase 2 MF cohort, tumors must have at least one of the
following FGFR3 mutations: R248C, S249C, G370/2C, S371/3C, Y373/5C, G380/82R,
F384/6L, K650/2X (X<=E,T or M) or FGFR3- TACC3 fusion, as shown by tests
performed by a CAP or CLIA certified laboratory (or equivalent outside of the
US) on samples that were obtained at or after the time when the subject was
found to have muscle invasive / metastatic disease or high grade papillary
non-muscle invasive disease.
In the absence of pre-existing genetic test results, subjects can submit
archival tissue (obtained at or after the time subject was found to have muscle
invasive / metastatic disease) for genetic testing. If no suitable tissue is
available, a blood sample may be used to determine FGFR3 genetic status.
Subsequent to subject enrollment, blood samples used to determine FGFR3 status,
or previous test results that were not provided by Foundation Medicine will be
verified using archival tissue or the first biomarker tumor biopsy sample.
2. Have progression during or following platinum-containing chemotherapy in
metastatic setting or within 12 months of neoadjuvant or adjuvant treatment
with platinum-containing chemotherapy
OR
Have a PD-L1 positive tumor (per label) at the time of metastatic disease, and
are not eligible for cisplatin-containing chemotherapy defined as meeting any
of the following criteria:
- Creatinine clearance <60 mL/min (GFR by direct measurement, or using
Cockcroft-Gault equation)
- Equal to or greater than grade 2 hearing loss
- Equal to or greater than grade 2 peripheral neuropathy
- New York Heart Association Class III heart failure
3. Have available archival tumor or be willing to undergo diagnostic biopsy
during screening.
4. Have measurable disease according to Response Evaluation Criteria in Solid
Tumors Version 1.1 (RECIST v1.1).
5. Male and female subjects, age ? 18 years.
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) < 1 (see
Appendix 1).
7. Willingness to avoid pregnancy or fathering children based on the criteria
below:
a. Women of non-childbearing potential (i.e., surgically sterile with a
hysterectomy and/or bilateral oophorectomy OR chemically sterile OR ? 12 months
of amenorrhea in the absence of chemotherapy, anti-estrogens, or ovarian
suppression). Women of non-childbearing potential need not undergo pregnancy
testing.
b. Women of childbearing potential who have a negative urine or serum pregnancy
test at Screening and before the first dose of study drug and who agree to take
appropriate precautions to avoid pregnancy (with approximately 99% certainty)
from Screening through 120 days after the last dose of study drug. Permitted
methods of contraception that are approximately 99% effective in preventing
pregnancy are described in Appendix 4, should be communicated to the subject,
and the subject*s understanding confirmed.
c. Men who agree to take appropriate precautions to avoid fathering children
(with at least 99% certainty) from Screening through

Exclusion Criteria

1. Participants with a history of idiopathic pulmonary fibrosis, organizing
pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of
active pneumonitis on the Screening chest CT scan.
2. Prior therapy with an anti-programmed cell death 1 (PD-1) or anti-PD-Ligand
1 agent, or with an agent directed to another co-inhibitory T-cell receptor or
FGFR inhibitor.
3. Patients with autoimmune disease or medical conditions that required
systemic corticosteroids (> 10 mg/day prednisone or its equivalent) or other
immunosuppressive medications or any other form of systemic immunosuppressive
therapy within 7 days prior to the first dose of study treatment. Note:
Replacement therapy (e.g. physiologic corticosteroid replacement therapy for
adrenal or pituitary insufficiency, etc.) is not considered a form of systemic
treatment.
4. Prior anti-cancer therapy (e.g. biologic or other targeted therapy,
chemotherapy or hormonal therapy) within 14 days prior to the first dose of
study treatment.
A washout of less than 14 days may be allowed after discussion with the Medical
Monitor, provided
that the subject has recovered from any clinically relevant toxicity
(Exception: participants with neuropathy of Grade 1 will be allowed study
entry).
5. Acute clinical AEs, except for alopecia, from any previous treatments must
have resolved to < Grade 1, or chronic defined as present for more than 6
months without worsening and not greater than Grade 2
6. Laboratory AEs from any previous treatments must have resolved to < Grade 1
or to within 10% of baseline prior to the first dose of study treatment.
7. Participants who are receiving or have received any other investigational
drugs or devices within 14 days prior to the first dose of study medications.
8. Participants with a diagnosis of immunodeficiency.
9. Primary central nervous system (CNS) malignancy or CNS metastases.
10. Participants with a history of allergic reactions attributed to monoclonal
antibody therapy (or recombinant antibody-related fusion proteins).
11. History of major bleeding (requiring a blood transfusion * 2 units) not
related to a tumor within the past 12 months.
12. History of clinically significant coagulation or platelet disorder in the
past 12 months.
13. Participants who have not recovered adequately from the toxicity and/or
complications from the interventions prior to starting therapy.
14. Incomplete healing from wounds from prior surgery (wounds larger than 2 cm
in length) within 28 days prior to the first dose of study treatment
15. Participants with an active uncontrolled infection requiring systemic
therapy (e.g., IV antibiotics or antifungal therapy).
Note: The use of oral anti-infectious agents for prophylaxis or treatment of
resolving infections is not considered exclusionary under this rule.
16. Participants who have received a live vaccine within 30 days of planned
start of study therapy.
Note: Seasonal influenza vaccines with inactivated flu vaccines are allowed;
however, live
attenuated vaccines such as intranasal influenza vaccines (e.g., Flu-Mist®) are
not allowed.
17. Participants with uncontrolled intercurrent illness including, but not
limited to, ongoing or symptomatic congestive heart failure, unstable angina
pectoris, or psychiatric illness/social situations that

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Endpoint Phase 1b:<br /><br>*DLTs within the 35-day observation period.<br /><br><br /><br>Endpoints Phase 2:<br /><br><br /><br>Primary Endpoints:<br /><br>*Determine the relationship between the level of FGFR3 receptor expression and<br /><br>the expression of markers<br /><br>of FGFR3 pathway inhibition as measured by gene expression profiling (using a<br /><br>technique such as whole<br /><br>transcriptome RNAseq) or immunohistochemistry on biopsies taken pre- and<br /><br>post-vofatamab treatment.<br /><br>*Safety and tolerability assessed through summariesmeasurements of AEs,<br /><br>physical examination findings,<br /><br>laboratory test results, and vital signs over time.</p><br>