Meeting of the Oncologic Drugs Advisory Committee Meeting Announcement

Date:

March 15, 2024

Time:

8:30 AM - 5:30 PM ET

What is an advisory committee?

Advisory committees provide independent expert advice to the FDA on broad scientific topics or on certain products to help the agency make sound decisions based on the available science. Advisory committees make non-binding recommendations to the FDA, which generally follows the recommendations but is not legally bound to do so. Please see, "Advisory Committees Give FDA Critical Advice and the Public a Voice," for more information.

YouTube Broadcast of the Meeting: Oncologic Drugs Advisory Committee (ODAC) Live Video

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Center: Center for Drug Evaluation and Research

Location: All meeting participants will be heard, viewed, captioned, and recorded for this advisory committee meeting via an online teleconferencing and/or video conferencing platform.

Agenda

The meeting presentations will be heard, viewed, captioned, and recorded through an online teleconferencing platform. During the morning session, the Committee will discuss supplemental biologics license application (sBLA) 125746.74 for CARVYKTI (ciltacabtagene autoleucel), suspension for intravenous infusion, submitted by Janssen Biotech, Inc. The proposed indication for this product is for the treatment of adult patients with relapsed or refractory multiple myeloma, who have received at least one prior line of therapy, including a proteasome inhibitor, and an immunomodulatory agent, and are refractory to lenalidomide. The Committee will have a general discussion focused on the overall survival data in the Study MMY3002 (CARTITUDE-4) and the risk and benefit of ciltacabtagene autoleucel in the intended population. During the afternoon session, the Committee will discuss sBLA 125736.218 for ABECMA (idecabtagene vicleucel), suspension for intravenous infusion, submitted by Celgene Corp., a Bristol-Myers Squibb Co. The proposed indication is for the treatment of adult patients with relapsed or refractory multiple myeloma who have received an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. The Committee will have a general discussion focused on the overall survival data in the Study MM-003 (KarMMa-3) and the risk and benefit of idecabtagene vicleucel in the intended population.

Meeting Materials

FDA intends to make background material and the link to the live webcast available to the public no later than two (2) business days before the meeting in the Event Materials section of this web page. If FDA is unable to post the background material on its website prior to the meeting, the background material will be made publicly available on FDA’s website at the time of the advisory committee meeting. The meeting will include slide presentations with audio components to allow the presentation of materials in a manner that most closely resembles an in-person advisory committee meeting.

Public Participation Information

Interested persons may present data, information, or views, orally or in writing, on issues pending before the committee.

FDA is establishing a docket for public comment on this meeting. The docket number is FDA-2024-N-0018. Please note that late, untimely filed comments will not be considered. The docket will close on March 14, 2024. The https://www.regulations.gov electronic filing system will accept comments until 11:59 p.m. Eastern Time at the end of March 14, 2024. Comments received by mail/hand delivery/courier (for written/paper submissions) will be considered timely if they are received on or before that date.

Comments received on or before March 1, 2024 will be provided to the Committee. Comments received after that date will be taken into consideration by FDA. In the event that the meeting is cancelled, FDA will continue to evaluate any relevant applications or information, and consider any comments submitted to the docket, as appropriate. You may submit comments as follows:

Electronic Submissions

Submit electronic comments in the following way:

• Federal eRulemaking Portal: https://www.regulations.gov. Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to https://www.regulations.gov will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else’s Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on https://www.regulations.gov.

• If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed (see “Written/Paper Submissions” and “Instructions”).

Written/Paper Submissions

Submit written/paper submissions as follows:

• Mail/Hand delivery/Courier (for written/paper submissions): Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

• For written/paper comments submitted to the Dockets Management Staff, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in “Instructions.”

Instructions: All submissions received must include the Docket No. FDA-2024-N-0018 for “Oncologic Drugs Advisory Committee; Notice of Meeting; Establishment of a Public Docket.” Received comments, those filed in a timely manner, will be placed in the docket and, except for those submitted as “Confidential Submissions,” publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.

• Confidential Submissions--To submit a comment with confidential information that you do not wish to be made publicly available, submit your comments only as a written/paper submission. You should submit two copies total. One copy will include the information you claim to be confidential with a heading or cover note that states “THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.” FDA will review this copy, including the claimed confidential information, in its consideration of comments. The second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on https://www.regulations.gov. Submit both copies to the Dockets Management Staff. If you do not wish your name and contact information be made publicly available, you can provide this information on the cover sheet and not in the body of your comments and you must identify the information as “confidential.” Any information marked as “confidential” will not be disclosed except in accordance with 21 CFR 10.20 and other applicable disclosure law. For more information about FDA’s posting of comments to public dockets, see 80 FR 56469, September 18, 2015, or access the information at: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.

Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in the heading of this document, into the “Search” box and follow the prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, 240-402-7500.

Oral Presentations

Oral presentations from the public will be scheduled between approximately 11:10 a.m. to 11:40 a.m. and 4 p.m. to 4:30 p.m. Eastern Time. Those individuals interested in making formal oral presentations should notify the contact person and submit a brief statement of the general nature of the evidence or arguments they wish to present, the names and addresses of proposed participants, and an indication of the approximate time requested to make their presentation on or before February 22, 2024.

Time allotted for each presentation may be limited. If the number of registrants requesting to speak is greater than can be reasonably accommodated during the scheduled open public hearing session, FDA may conduct a lottery to determine the speakers for the scheduled open public hearing session. The contact person will notify interested persons regarding their request to speak by February 23, 2024.

Webcast Information

CDER plans to provide a free of charge, live webcast of the upcoming advisory committee meeting. If there are instances where the webcast transmission is not successful, staff will work to re-establish the transmission as soon as possible. Further information regarding the webcast, including the web address for the webcast, will be made available no later than two (2) business days before the meeting in the Event Materials section of this web page. CDER plans to post archived webcasts after the meeting, however, in cases where transmission was not successful, archived webcasts will not be available.

Contact Information

• Joyce Frimpong, PharmD
  Center for Drug Evaluation and Research
  Food and Drug Administration
  10903 New Hampshire Avenue
  WO31-2417
  Silver Spring, MD 20993-0002
  
  Phone: 301-796-7973
  Email: ODAC@fda.hhs.gov

• FDA Advisory Committee Information Line
  1-800-741-8138
  (301-443-0572 in the Washington DC area)
  Please call the Information Line for up-to-date information on this hearing.

• For press inquiries, please contact the Office of Media Affairs at Email: fdaoma@fda.hhs.gov or 301–796–4540

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Notice of this meeting is given under the Federal Advisory Committee Act (5 U.S.C. app.2).

FDA grants accelerated approval to zanubrutinib for r/r follicular lymphoma

On March 7, 2024, the Food and Drug Administration granted accelerated approval to zanubrutinib (Brukinsa, BeiGene USA, Inc.) with obinutuzumab for relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy.

Full prescribing information for Brukinsa will be posted here.

The regimen was evaluated in Study BGB-3111-212 (ROSEWOOD; NCT03332017), an open-label, multicenter, randomized trial that enrolled 217 adult patients with relapsed or refractory FL after at least 2 prior systemic treatments. Patients were randomized (2:1) to receive either zanubrutinib 160 mg orally twice daily until disease progression or unacceptable toxicity plus obinutuzumab (ZO), or obinutuzumab alone. The median number of prior lines of therapy was 3 (range 2-11).

Efficacy was based on overall response rate (ORR) and duration of response (DOR) determined by an independent review committee. ORR was 69% (95% CI: 61, 76) in the ZO arm and 46% (95% CI: 34, 58) in the obinutuzumab arm (two-sided p-value, 0.0012). With a median follow-up of 19.0 months, the median DOR was not reached in the ZO arm (95% CI: 25.3 months, NE) and was 14.0 months (95% CI: 9.2, 25.1) for those patients receiving obinutuzumab monotherapy. The estimated DOR rate at 18 months was 69% (95% CI: 58, 78) in the ZO arm.

Across clinical trials of zanubrutinib, the most common adverse reactions (≥30%), including laboratory abnormalities, were decreased neutrophil counts (51%) and platelet counts (41%), upper respiratory tract infection (38%), hemorrhage (32%), and musculoskeletal pain (31%). Serious adverse reactions occurred in 35% of patients with FL who received ZO.

The recommended zanubrutinib dosage is 160 mg taken orally twice daily or 320 mg taken orally once daily until disease progression or unacceptable toxicity.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

This application was granted fast track designation and orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

FDA approves Pfizer’s inotuzumab ozogamicin for pediatric patients with acute lymphoblastic leukemia

On March 6, 2024, the Food and Drug Administration approved inotuzumab ozogamicin (Besponsa, Pfizer) for pediatric patients 1 year and older with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia (ALL).

Full prescribing information for Besponsa will be posted here.

Efficacy was evaluated in a multicenter, single-arm, open-label study in 53 pediatric patients 1 year and older with relapsed or refractory CD22-positive B-cell precursor ALL. Two dose levels were evaluated--an initial dose of 1.4 mg/m2/cycle in 12 patients and 1.8 mg/m2/cycle in 41 patients. Premedications included methylprednisolone 1 mg/kg (maximum of 50 mg), an antipyretic, and an antihistamine. Patients received a median of 2 cycles of therapy (range: 1 to 4 cycles).

The main efficacy outcome measures were complete remission (CR), duration of CR, and the proportion of patients with minimal residual disease (MRD) negative CR. CR was defined as < 5% blasts in the bone marrow and the absence of peripheral blood leukemia blasts, full recovery of peripheral blood counts (platelets ≥ 100 × 109 and ANC ≥1 × 109/L), and resolution of any extramedullary disease. MRD was defined by leukemic cells comprising < 1 × 10-4 (<0.01%) of bone marrow nucleated cells by flow cytometry or by PCR.

In all patients, 22/53 (42%, 95% CI: 28.1, 55.9%) achieved CR and the median duration of CR was 8.2 months (95% CI: 2.6, NE). The MRD negativity rate in patients with CR was 21/22 [95.5% (95% CI: 77.2, 99.9)] based on flow cytometry, and 19/22 [86.4% (95% CI: 65.1, 97.1] based on RQ-PCR.

The most common adverse reactions (≥20%), including laboratory abnormalities, were thrombocytopenia, pyrexia, anemia, vomiting, infection, hemorrhage, neutropenia, nausea, leukopenia, febrile neutropenia, increased transaminases, abdominal pain, and headache.

For the first cycle, the recommended inotuzumab ozogamicin dose is 1.8 mg/m2 per cycle, administered as 3 divided doses on Day 1 (0.8 mg/m2), Day 8 (0.5 mg/m2), and Day 15 (0.5 mg/m2). Cycle 1 is 3 weeks in duration but may be extended to 4 weeks if the patient achieves a complete remission or complete remission with incomplete hematologic recovery, and/or to allow recovery from toxicity. See the prescribing information for the recommended dosage after the first cycle.

This application was granted priority review and orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

FDA approves amivantamab in first-line EGFR exon 20 insertion-mutated non-small cell lung cancer indications; converts to traditional approval

On March 1, 2024, the Food and Drug Administration approved amivantamab-vmjw (Rybrevant, Janssen Biotech, Inc.) with carboplatin and pemetrexed for the first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test.

The FDA also granted traditional approval to amivantamab-vmjw for adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. FDA previously granted accelerated approval for this indication.

Full prescribing information for Rybrevant will be posted here.

Efficacy was evaluated in PAPILLON (NCT04538664), a randomized, open-label multicenter trial of 308 patients with EGFR exon 20 insertion mutations. Patients were randomized 1:1 to receive amivantamab-vmjw with carboplatin and pemetrexed or carboplatin and pemetrexed.

The major efficacy outcome measure was progression-free survival (PFS) as assessed by blinded independent central review (BICR), with overall survival (OS) as a key secondary outcome measure. Amivantamab-vmjw plus carboplatin and pemetrexed demonstrated a statistically significant improvement in PFS compared with carboplatin and pemetrexed with a hazard ratio of 0.40 (95% CI: 0.30, 0.53; p-value<0.0001). The median PFS was 11.4 months (95% CI: 9.8, 13.7) and 6.7 months (95% CI: 5.6, 7.3) in the respective arms.

While OS results were immature at the current analysis, with 44% of pre-specified deaths for the final analysis reported, no trend towards a detriment was observed.

The most common adverse reactions (≥20%) were rash, nail toxicity, stomatitis, infusion-related reaction, fatigue, edema, constipation, decreased appetite, nausea, COVID-19, diarrhea, and vomiting.

The recommended amivantamab-vmjw dose is based on body weight. See the prescribing information for specific dosage information.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Brazilian Health Regulatory Agency (ANVISA) and Health Canada. The application reviews are ongoing at the other regulatory agencies.

This review used the Real-Time Oncology Review (RTOR) pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application four weeks ahead of the FDA goal date.

This application was granted priority review. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Iovance’s AMTAGVI™ (lifileucel) Receives U.S. FDA Accelerated Approval for Advanced Melanoma

On February 16, 2024, the Food and Drug Administration granted accelerated approval to lifileucel (Amtagvi, Iovance Biotherapeutics, Inc.), a tumor-derived autologous T cell immunotherapy, for adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 positive, a BRAF inhibitor with or without a MEK inhibitor.

Full prescribing information for Amtagvi will be posted here.

Safety and efficacy were evaluated in a global, multicenter, multicohort, open-label, single-arm trial in patients with unresectable or metastatic melanoma who had previously been treated with at least one systemic therapy, including a PD-1 blocking antibody, and if BRAF V600 mutation-positive, a BRAF inhibitor with or without a MEK inhibitor. Among 89 patients who received lifileucel, two patients were excluded because the product did not meet specification and five patients were excluded due to product comparability. Lifileucel was administered following a lymphodepleting regimen consisting of cyclophosphamide 60 mg/kg daily with mesna for 2 days followed by fludarabine 25 mg/m2 daily for 5 days. Three to 24 hours after infusion, patients received IL-2 (aldesleukin) at 600,000 IU/kg every 8 to 12 hours for up to 6 doses in order to support cell expansion in vivo. The median administered lifileucel dose was 21.1× 109 viable cells. The median number of administered IL-2 (aldesleukin) doses was 6.

The main efficacy outcome measures were objective response rate (ORR) and duration of response (DoR). The median time to initial response to lifileucel was 1.5 months. ORR was based on 73 subjects who received lifileucel within the recommended dosing range of 7.5 x109 to 72x109 viable cells. ORR was 31.5% (95% CI: 21.1, 43.4) and median DoR was not reached (NR) (95% CI: 4.1 months, NR).

The prescribing information contains a Boxed Warning for treatment-related mortality, prolonged severe cytopenia, severe infection, cardiopulmonary, and renal impairment. The most common adverse reactions (≥20%) in order of decreasing frequency were chills, pyrexia, fatigue, tachycardia, diarrhea, febrile neutropenia, edema, rash hypotension, alopecia, infection, hypoxia, and dyspnea.

The recommended lifileucel dose is 7.5 x 109 to 72 x 109 viable cells.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

This application was granted priority review, fast track designation, Regenerative Medicine Advanced Therapy designation, and orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

FDA converts 2021 accelerated approval of tepotinib (EMD Serono, Inc.) in MET exon 14 NSCLC

FDA approves tepotinib for metastatic non-small cell lung cancer

On February 15, 2024, the Food and Drug Administration granted traditional approval to tepotinib (Tepmetko, EMD Serono, Inc.) for adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations.

Full prescribing information for Tepmetko will be posted here.

Tepotinib was previously granted accelerated approval for this indication on February 3, 2021, based on initial overall response rate (ORR) and duration of response (DOR) in the VISION trial (NCT02864992), a multicenter, non-randomized, open-label, multicohort study. The conversion to traditional approval was based on an additional 161 patients and an added 28 months of follow-up time to assess DOR. 

Efficacy was demonstrated in a total of 313 patients with metastatic NSCLC harboring MET exon skipping alterations. Patients received tepotinib 450 mg once daily until disease progression or unacceptable toxicity.

The primary efficacy measures were ORR and DOR, determined by a Blinded Independent Review Committee. Among 164 treatment-naïve patients, ORR was 57% (95% CI: 49, 65), with 40% of responders having a DOR ≥12 months. Among 149 previously treated patients, ORR was 45% (95% CI: 37, 53), with 36% of responders having a DOR ≥12 months.

The most common adverse reactions (≥20%) were edema, nausea, fatigue, musculoskeletal pain, diarrhea, dyspnea, decreased appetite, and rash.

The recommended tepotinib dose is 450 mg orally once daily with food.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

This application was granted breakthrough designation and orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

FDA approve Ipsen's Onivyde for the first-line treatment of metastatic pancreatic adenocarcinoma

On February 13, 2024, the Food and Drug Administration approved irinotecan liposome (Onivyde, Ipsen Biopharmaceuticals, Inc.) with oxaliplatin, fluorouracil, and leucovorin, for the first-line treatment of metastatic pancreatic adenocarcinoma.

Full prescribing information for Onivyde will be posted here.

Efficacy was evaluated in NAPOLI 3 (NCT04083235), a randomized, multicenter, open-label, active-controlled trial in 770 patients with metastatic pancreatic adenocarcinoma who had not previously received chemotherapy in the metastatic setting. Randomization was stratified by region, liver metastases, and ECOG performance status. Patients were randomized (1:1) to receive one of the following treatments:

• NALIRIFOX: irinotecan liposome 50 mg/m2 as an intravenous infusion over 90 minutes, followed by oxaliplatin 60 mg/m2 as an intravenous infusion over 120 minutes, followed by leucovorin 400 mg/m2 intravenously over 30 minutes, followed by fluorouracil 2400 mg/m2 intravenously over 46 hours, every 2 weeks.

• Gem+NabP: Nab-paclitaxel 125 mg/m2 as an intravenous infusion over 35 minutes, followed by gemcitabine 1000 mg/m2 intravenously over 30 minutes on days 1, 8, and 15 of each 28-day cycle.

The main efficacy outcome measure was overall survival (OS). Additional efficacy measures were investigator-assessed progression-free survival (PFS) and objective response rate (ORR). NAPOLI 3 demonstrated a statistically significant improvement in OS and PFS for the NALIRIFOX arm over the Gem+NabP arm. Median OS was 11.1 months (95% CI: 10.0, 12.1) in the NALIRIFOX arm and 9.2 months (95% CI: 8.3, 10.6) in the Gem+NabP arm (Hazard Ratio [HR] 0.84 [95% CI: 0.71, 0.99]; p-value 0.0403). Median PFS was 7.4 months (95% CI: 6.0, 7.7) in the NALIRIFOX arm and 5.6 months (95% CI: 5.3, 5.8) in the Gem+NabP arm (HR 0.70 [95% CI: 0.59, 0.85]; p-value 0.0001). ORR was 41.8% (95% CI: 36.8, 46.9) in the NALIRIFOX arm and 36.2% (95% CI: 31.4, 41.2) in the Gem+NabP arm.

The most common adverse reactions of NALIRIFOX (≥20% with a difference between arms of ≥5% for all grades or ≥2% for Grades 3 or 4 compared to Gem+NabP) were diarrhea, fatigue, nausea, vomiting, decreased appetite, abdominal pain, mucosal inflammation, constipation, and decreased weight. The most common laboratory abnormalities (≥10% Grade 3 or 4) were decreased neutrophils, decreased potassium, decreased lymphocyte, and decreased hemoglobin.

The recommended irinotecan liposome dose is 50 mg/m2 administered by intravenous infusion over 90 minutes every 2 weeks. Administer irinotecan liposome before oxaliplatin, fluorouracil, and leucovorin. There is no recommended dosage of irinotecan liposome for patients with serum bilirubin above the upper limit of normal.

This application was granted orphan drug designation.

FDA Grants Full Approval for BALVERSA® to Treat Locally Advanced or Metastatic Bladder Cancer with Select Genetic Alterations

BALVERSA® is the First and Only Targeted Therapy for Patients with Locally Advanced or Metastatic Urothelial Carcinoma and Susceptible Fibroblast Growth Factor Receptor Alterations 

Phase 3 THOR Study Showed a 36 Percent Reduction in the Risk of Death with BALVERSA® Versus Chemotherapy in Patients

Data were featured at the European Society for Medical Oncology (ESMO) 2023 Congress and in The New England Journal of Medicine

RARITAN, N.J., JANUARY 19, 2024 – Johnson & Johnson announced today that the U.S. Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) for BALVERSA® (erdafitinib) for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (mUC) with susceptible fibroblast growth factor receptor 3 (FGFR3) genetic alterations whose disease has progressed on or after at least one line of prior systemic therapy. BALVERSA® is not recommended for the treatment of patients who are eligible for and have not received prior PD-1 or PD-L1 inhibitor therapy. This FDA action converts the April 2019 accelerated approval of BALVERSA® to a full approval based on the clinical and overall survival benefit observed in the Phase 3 THOR study. BALVERSA® is the first oral FGFR kinase inhibitor to be approved, and the first and only targeted treatment for patients with mUC and FGFR alterations.

Approximately 20 percent of patients with mUC have FGFR3 genetic alterations. After one or more lines of systemic therapy, including a checkpoint inhibitor, these patients generally have a poor prognosis with few available treatment options. This approval is based on results from Cohort 1 of the randomized, controlled, open-label, multicenter Phase 3 THOR study (NCT03390504) confirming the clinical benefit of BALVERSA® in extending overall survival (OS) compared to chemotherapy in the second-line setting. Results from the study showed a 36 percent reduction in the risk of death with BALVERSA® versus chemotherapy in patients previously treated with a PD-1 or PD-(L)1 inhibitor, with those in the BALVERSA® arm living a median of over four months longer (Hazard Ratio (HR) 0.64; [95 percent Confidence Interval (CI), 0.47-0.88]; p=0.0050).1

“Based on results from randomized Phase 3 data, BALVERSA continues to demonstrate the promise of targeted therapy in the treatment of patients with advanced bladder cancer,” said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Johnson & Johnson Innovative Medicine. “This important milestone reinforces our commitment to advance innovative, precision therapies in oncology and confirm the role of targeted therapy in the treatment of bladder cancer.”

Warnings and Precautions in the U.S. Prescribing Information include ocular disorders, hyperphosphatemia and embryo-fetal toxicity. The most common (>20%) adverse reactions, including laboratory abnormalities, were increased phosphate, nail disorders, stomatitis, diarrhea, increased creatinine, increased alkaline phosphate, increased alanine aminotransferase, decreased hemoglobin, decreased sodium, increased aspartate aminotransferase, fatigue, dry mouth, dry skin, decreased phosphate, decreased appetite, dysgeusia, constipation, increased calcium, dry eye, palmar-plantar erythrodysesthesia syndrome, increased potassium, alopecia, and central serous retinopathy.2

Johnson & Johnson is offering BALVERSA® and associated patient services through a single-source specialty pharmacy provider, US Bioservices. This model is part of the Company’s ongoing commitment to provide high-quality products, services, access, and support to healthcare professionals and patients.

The current full Prescribing Information is available at www.BALVERSA.com.

About THOR

THOR (NCT03390504) is a Phase 3 randomized, open-label, multicenter study evaluating the efficacy and safety of BALVERSA®. All patients included in the study had metastatic or unresectable UC, with selected FGFR genetic alterations, and showed disease progression during or after one or two prior lines of treatment. The study compared BALVERSA® in two cohorts; BALVERSA® versus standard of care chemotherapy (investigator’s choice of docetaxel or vinflunine) after at least one line of treatment including an anti-programmed death (ligand) 1 (PD-[L]1) agent (Cohort 1); and BALVERSA® compared to pembrolizumab after one prior treatment not containing an anti-PD-(L)1 agent (Cohort 2). The trial consists of screening, a treatment phase (from randomization until disease progression, intolerable toxicity, withdrawal of consent or decision by investigator to discontinue treatment) and a post-treatment follow-up (from end-of-treatment to participant’s death, withdraws consent, or lost to follow-up study completion for the respective cohort, whichever comes first). A long-term extension period is planned for after the clinical cutoff date is achieved for the final analysis of each cohort for patients who continue to benefit from the study intervention. The primary endpoint of the study is OS; progression free survival (PFS), objective response rate (ORR), duration of response (DOR), patient-reported outcomes, safety, and pharmacokinetics (PK) are secondary endpoints.

Results from Cohort 1 were presented in a Late-Breaking Presentation Session (Abstract #LBA4619) at the 2023 American Society of Clinical Oncology Annual Meeting.[1]  In June 2023, based on the recommendation of the independent data safety monitoring committee, the THOR study was stopped at the interim analysis for efficacy and all patients randomized to chemotherapy were offered the opportunity to cross over to BALVERSA®. Results from Cohort 1 and Cohort 2 of the confirmatory, Phase 3, randomized study were presented at ESMO 2023 (Abstract #2359O), and results of Cohort 1 were published in the New England Journal of Medicine in November 2023.

About BALVERSA®

BALVERSA® (erdafitinib) is a once-daily, oral FGFR kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (mUC) with susceptible fibroblast growth factor receptor 3 (FGFR3) genetic alterations whose disease progressed on or after at least one line of prior systemic therapy. BALVERSA ® is not recommended for the treatment of patients who are eligible for and have not received prior PD-1 or PD-(L)1 inhibitor therapy.[2]  Patients are selected for therapy based on an FDA-approved companion diagnostic for BALVERSA®. Information on FDA-approved tests for the detection of FGFR genetic alterations in urothelial cancer is available at: http://www.fda.gov/CompanionDiagnostics.

BALVERSA® received Breakthrough Therapy Designation from the U.S. FDA in 2018 and received accelerated approval in 2019 for the treatment of adults with locally advanced or mUC which has susceptible FGFR3 or FGFR2 genetic alterations and who have progressed during or following at least one line of prior platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.[3]

The Company submitted a marketing authorization application to the European Medicines Agency in September 2023 for BALVERSA ® as a treatment for adult patients with FGFR3-altered, locally advanced unresectable or metastatic urothelial carcinoma that has progressed following therapy with a PD-(L)1 inhibitor.

In 2008, Janssen Pharmaceuticals entered into an exclusive worldwide license and collaboration agreement with Astex Pharmaceuticals to develop and commercialize BALVERSA®.

For more information, visit www.BALVERSA.com.

About Urothelial Carcinoma

Urothelial carcinoma, also known as transitional cell carcinoma, starts in the innermost lining of the bladder.[4] It is the most common form of bladder cancer, representing more than 90 percent of all bladder cancers.[5] Metastatic or unresectable disease is identified in approximately 20 percent of patients presenting with urothelial cancer, and an estimated five to eight percent of all bladder cancers. Approximately one in five patients (20 percent) diagnosed with mUC have an FGFR genetic alteration.[6],[7] Fibroblast growth factor receptors are a family of receptor tyrosine kinases that can be activated by genetic alterations in a variety of tumor types, and these alterations may lead to increased tumor cell growth and survival. 6,[8],[9],[10],[11] Select FGFR genetic alterations can be detected through an FDA-approved companion diagnostic. The five-year survival rate for patients with Stage IV metastatic bladder cancer that has spread to distant parts of the body is currently eight percent.[12]

BALVERSA® IMPORTANT SAFETY INFORMATION

WARNING AND PRECAUTIONS

Ocular Disorders – BALVERSA® can cause ocular disorders, including central serous retinopathy/retinal pigment epithelial detachment (CSR/RPED) resulting in visual field defect.

CSR/RPED occurred in 22% of patients treated with BALVERSA, with a median time to first onset of 46 days. In 104 patients with CSR, 40% required dose interruptions and 56% required dose reductions; 2.9% of BALVERSA-treated patients required permanent discontinuation for CSR. Of the 24 patients who restarted BALVERSA after dose interruption with or without dose reduction, 67% had recurrence and/or worsening of CSR after restarting. CSR was ongoing in 41% of the 104 patients at the time of last evaluation.

Dry eye symptoms occurred in 26% of BALVERSA®-treated patients. All patients should receive dry eye prophylaxis with ocular demulcents as needed.

Perform monthly ophthalmological examinations during the first 4 months of treatment and every 3 months afterwards, and urgently at any time for visual symptoms. Ophthalmological examination should include assessment of visual acuity, slit lamp examination, fundoscopy, and optical coherence tomography. Withhold or permanently discontinue BALVERSA® based on severity and/or ophthalmology exam findings [see Dosage and Administration (2.3)].

Hyperphosphatemia and Soft Tissue Mineralization – BALVERSA® can cause hyperphosphatemia leading to soft tissue mineralization, cutaneous calcinosis, non-uremic calciphylaxis and vascular calcification. Increases in phosphate levels are a pharmacodynamic effect of BALVERSA® [see Pharmacodynamics (12.2)].  Increased phosphate occurred in 73% of BALVERSA®-treated patients. The median onset time of increased phosphate was 16 days (range: 8–421) after initiating BALVERSA®. Twenty-four percent of patients received phosphate binders during treatment with BALVERSA®. Vascular calcification was observed in 0.2% of patients treated with BALVERSA®.

Monitor for hyperphosphatemia throughout treatment. In all patients, restrict phosphate intake to 600‑800 mg daily and avoid concomitant use of agents that may increase serum phosphate levels. If serum phosphate is above 7.0 mg/dL, consider adding an oral phosphate binder until serum phosphate level returns to <7.0 mg/dL. Withhold, dose reduce, or permanently discontinue BALVERSA® based on duration and severity of hyperphosphatemia [see Dosage and Administration (2.3), Table 2: Dose Modifications for Adverse Reactions].

Embryo-Fetal Toxicity – Based on the mechanism of action and findings in animal reproduction studies, BALVERSA® can cause fetal harm when administered to a pregnant female. In a rat embryo-fetal toxicity study, erdafitinib caused malformations and embryo-fetal death at maternal exposures that were less than the human exposures at the maximum human recommended dose. Advise pregnant patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment with BALVERSA® and for one month after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with BALVERSA® and for one month after the last dose [see Use in Specific Populations (8.1, 8.3) and Clinical Pharmacology (12.1)].

Adverse Reactions

In this pooled safety population of 479 patients who received BALVERSA®, the median duration of treatment was 4.8 months (range: 0.1 to 43 months). The most common (>20%) adverse reactions were: increased phosphate, nail disorders, stomatitis, diarrhea, increased creatinine, increased alkaline phosphatase, increased alanine aminotransferase, decreased hemoglobin, decreased sodium, increased aspartate aminotransferase, fatigue, dry mouth, dry skin, decreased phosphate, decreased appetite, dysgeusia, constipation, increased calcium, dry eye, palmar-plantar erythrodysesthesia syndrome, increased potassium, alopecia, and central serous retinopathy.

In Cohort 1 of the BLC3001 study:

• Serious adverse reactions occurred in 41% of patients who received BALVERSA®. Serious reactions in >2% of patients included urinary tract infection (4.4%), hematuria (3.7%), hyponatremia (2.2%), and acute kidney injury (2.2%). Fatal adverse reactions occurred in 4.4% of patients who received BALVERSA®, including sudden death (1.5%), pneumonia (1.5%), renal failure (0.7%), and cardiorespiratory arrest (0.7%).

• Permanent discontinuation of BALVERSA® due to an adverse reaction occurred in 14% of patients. Adverse reactions which resulted in permanent discontinuation of BALVERSA® in >2% of patients included nail disorders (3%) and eye disorders (2.2%).

• Dosage interruptions of BALVERSA® due to an adverse reaction occurred in 72% of patients. Adverse reactions which required dosage interruption in >4% of patients included nail disorders (22%), stomatitis (19%), eye disorders (16%), palmar-plantar erythrodysesthesia syndrome (15%), diarrhea (10%), hyperphosphatemia (7%), increased aspartate aminotransferase (6%), and increased alanine aminotransferase (5%).

• Dose reductions of BALVERSA® due to an adverse reaction occurred in 69% of patients. Adverse reactions which required dose reductions in >4% of patients included nail disorders (27%), stomatitis (19%), eye disorders (17%), palmar-plantar erythrodysesthesia syndrome (12%), diarrhea (7%), dry mouth (4.4%), and hyperphosphatemia (4.4%).

• Clinically relevant adverse reactions in <15% of patients who received BALVERSA® included nausea (15%), pyrexia (15%), epistaxis (13%), vomiting (10%), and arthralgia (10%).

Drug Interactions

• Moderate CYP2C9 or Strong CYP3A4 Inhibitors: Consider alternative agents; however, if co-administration is unavoidable monitor closely for adverse reactions. (7.1)

• Strong CYP3A4 inducers: Avoid co-administration use with BALVERSA®. (7.1)

• Moderate CYP3A4 inducers: If co-administration is required at the start of BALVERSA® treatment, administer BALVERSA® at a dose of 9 mg daily.  (7.1)

• Serum phosphate level-altering agents: Avoid co-administration use with agents that can alter serum phosphate levels before the initial dose modification period based on serum phosphate levels. (2.3, 7.1)

• P-gp substrates: If co-administration is unavoidable separate BALVERSA® administration by at least 6 hours before or after administration of P-gp substrates with narrow therapeutic indices. (7.2)

Use in Specific Populations

Lactation – Because of the potential for serious adverse reactions from erdafitinib in a breastfed child, advise lactating patients not to breastfeed during treatment with BALVERSA® and for one month following the last dose.

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