BAVENCIO (Page 6 of 7)

14.3 Advanced Renal Cell Carcinoma

The efficacy and safety of BAVENCIO in combination with axitinib was demonstrated in the JAVELIN Renal 101 trial (NCT02684006), a randomized, multicenter, open-label, study of BAVENCIO in combination with axitinib in 886 patients with untreated advanced RCC regardless of tumor PD-L1 expression [intent-to-treat (ITT) population]. Patients with autoimmune disease or conditions requiring systemic immunosuppression were excluded.

Randomization was stratified according to Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (0 vs. 1) and region (United States vs. Canada/Western Europe vs. the rest of the world). Patients were randomized (1:1) to one of the following treatment arms:

  • BAVENCIO 10 mg/kg intravenous infusion every 2 weeks in combination with axitinib 5 mg twice daily orally (N=442). Patients who tolerated axitinib 5 mg twice daily without Grade 2 or greater axitinib-related adverse events for 2 consecutive weeks could increase to 7 mg and then subsequently to 10 mg twice daily. Axitinib could be interrupted or reduced to 3 mg twice daily and subsequently to 2 mg twice daily to manage toxicity.
  • Sunitinib 50 mg once daily orally for 4 weeks followed by 2 weeks off (N=444) until radiographic or clinical progression or unacceptable toxicity.

Treatment with BAVENCIO and axitinib continued until RECIST v1.1-defined progression of disease by Blinded Independent Central Review (BICR) assessment or unacceptable toxicity. Administration BAVENCIO and axitinib was permitted beyond RECIST-defined disease progression if the patient was clinically stable and considered to be deriving clinical benefit by the investigator. Assessment of tumor status was performed at baseline, after randomization at 6 weeks, then every 6 weeks thereafter up to 18 months after randomization, and every 12 weeks thereafter until documented confirmed disease progression by BICR.

Baseline characteristics were a median age of 61 years (range: 27 to 88), 38% of patients were 65 years or older, 75% were male, 75% were White, and the ECOG PS was 0 (63%) or 1 (37%), respectively. Patient distribution by International Metastatic Renal Cell Carcinoma Database (IMDC) risk groups was 21% favorable, 62% intermediate, and 16% poor.

The major efficacy outcome measures were progression-free survival (PFS), as assessed by an BICR using RECIST v1.1 and overall survival (OS) in patients with PD-L1-positive tumors using a clinical trial assay (PD-L1 expression level ≥ 1%). Since PFS was statistically significant in patients with PD-L1-positive tumors [HR 0.61 (95% CI: 0.48, 0.79)], it was then tested in the ITT population and a statistically significant improvement in PFS in the ITT population was also demonstrated.

With a median overall survival follow-up of 19 months, overall survival data were immature with 27% deaths in the ITT population.

Efficacy results are presented in Table 12 and Figure 2.

Table 12: Efficacy Results from JAVELIN Renal 101 Trial — ITT
Efficacy Endpoints(Based on BICR Assessment)BAVENCIO plus Axitinib(N=442)Sunitinib(N=444)
BICR: Blinded Independent Central Review; CI: Confidence interval; NE: Not estimable.
*
p-value based on stratified log-rank.
Progression-Free Survival (PFS)
Events (%)180 (41)216 (49)
Median in months (95% CI)13.8 (11.1, NE)8.4 (6.9, 11.1)
Hazard ratio (95% CI)0.69 (0.56, 0.84)
2-sided p-value *0.0002
Confirmed Objective Response Rate (ORR)
Objective Response Rate n (%)227 (51.4)114 (25.7)
(95% CI)(46.6, 56.1)(21.7, 30.0)
Complete Response (CR) n (%)15 (3.4)8 (1.8)
Partial Response (PR) n (%)212 (48)106 (24)

Figure 2: K-M Estimates for PFS based on BICR Assessment – ITT

Figure 2
(click image for full-size original)

16 HOW SUPPLIED/STORAGE AND HANDLING

BAVENCIO (avelumab) Injection is a sterile, preservative-free, and clear, colorless to slightly yellow solution for intravenous infusion supplied as a single-dose vial of 200 mg/10 mL (20 mg/mL), individually packed into a carton (NDC 44087-3535-1).

Store refrigerated at 36°F to 46°F (2°C to 8°C) in original package to protect from light.

Do not freeze or shake the vial.

The vial stopper is not made with natural rubber latex.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Immune-Mediated Adverse Reactions

Inform patients of the risk of immune-mediated adverse reactions requiring corticosteroids or hormone replacement therapy, including, but not limited to:

  • Pneumonitis: Advise patients to contact their healthcare provider immediately for new or worsening cough, chest pain, or shortness of breath [see Warnings and Precautions (5.1)].
  • Hepatitis: Advise patients to contact their healthcare provider immediately for jaundice, severe nausea or vomiting, pain on the right side of abdomen, lethargy, or easy bruising or bleeding [see Warnings and Precautions (5.1)].
  • Colitis: Advise patients to contact their healthcare provider immediately for diarrhea or severe abdominal pain [see Warnings and Precautions (5.1)].
  • Endocrinopathies: Advise patients to contact their healthcare provider immediately for signs or symptoms of adrenal insufficiency, hypothyroidism, hyperthyroidism, and diabetes mellitus [see Warnings and Precautions (5.1)].
  • Nephritis with Renal Dysfunction: Advise patients to contact their healthcare provider immediately for signs or symptoms of nephritis including decreased urine output, blood in urine, swelling in ankles, loss of appetite, and any other symptoms of renal dysfunction [see Warnings and Precautions (5.1)].
  • Dermatologic Adverse Reactions: Advise patients to contact their healthcare provider immediately for signs or symptoms of skin rash, itchy skin, rash with tiny spots and bumps, reddening of skin, blisters or peeling [see Warnings and Precautions (5.1)].

Infusion-Related Reactions

Advise patients to contact their healthcare provider immediately for signs or symptoms of potential infusion-related reactions [see Warnings and Precautions (5.2)].

Complications of Allogeneic HSCT

Advise patients of the risk of post-allogeneic hematopoietic stem cell transplantation complications [see Warnings and Precautions (5.3)].

Major Adverse Cardiovascular Events

Advise patients receiving BAVENCIO in combination with axitinib to contact their healthcare provider immediately for signs or symptoms of cardiovascular events including but not limited to new or worsening chest discomfort, dyspnea, or peripheral edema [see Warnings and Precautions (5.4)].

Embryo-Fetal Toxicity

Advise females of reproductive potential that BAVENCIO can cause fetal harm. Instruct females of reproductive potential to use effective contraception during and for at least one month after the last dose of BAVENCIO [see Warnings and Precautions (5.5) and Use in Specific Populations (8.1, 8.3)].

Lactation

Advise nursing mothers not to breastfeed while taking BAVENCIO and for at least one month after the final dose [see Use in Specific Populations (8.2)].

Manufactured by:
EMD Serono, Inc.
Rockland, MA 02370
U.S.A.

Marketed by:
EMD Serono, Inc. and Pfizer Inc., NY, NY 10017

US License No: 1773

BAVENCIO is a trademark of Merck KGaA, Darmstadt, Germany

Product of Switzerland

This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: November 2020
MEDICATION GUIDE BAVENCIO® (buh-VEN-see-oh)(avelumab)injection
What is the most important information I should know about BAVENCIO?BAVENCIO is a medicine that may treat certain cancers by working with your immune system. BAVENCIO can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. You can have more than one of these problem at the same time. These problems may happen anytime during treatment or even after your treatment has ended.Call or see your healthcare provider right away if you get any new or worsening signs or symptoms, including:Lung problems.
  • cough
  • shortness of breath
  • chest pain
Intestinal problems.
  • diarrhea (loose stools) or more frequent bowel movements than usual
  • stools that are black, tarry, sticky, or have blood or mucus
  • severe stomach-area (abdomen) pain or tenderness
Liver problems.
  • yellowing of your skin or the whites of your eyes
  • severe nausea or vomiting
  • pain on the right side of your stomach-area (abdomen)
  • dark urine (tea colored)
  • bleeding or bruising more easily than normal
Hormone gland problems.
  • headache that will not go away or unusual headaches
  • eye sensitivity to light
  • eye problems
  • rapid heartbeat
  • increased sweating
  • extreme tiredness
  • weight gain or weight loss
  • feeling more hungry or thirsty than usual
  • urinating more often than usual
  • hair loss
  • feeling cold
  • constipation
  • your voice gets deeper
  • dizziness or fainting
  • changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness
Kidney problems.
  • decrease in your amount of urine
  • blood in your urine
  • swelling of your ankles
  • loss of appetite
Skin problems.
  • rash
  • itching
  • skin blistering or peeling
  • painful sores or ulcers in mouth or nose, throat, or genital area
  • fever or flu-like symptoms
  • swollen lymph nodes
Problems can also happen in other organs and tissues. These are not all of the signs or symptoms of immune system problems that can happen with BAVENCIO. Call or see your healthcare provider right away for any new or worsening signs or symptoms, which may include:
  • Chest pain, irregular heartbeat, shortness of breath or swelling of ankles
  • Confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs
  • Double vision, blurry vision, sensitivity to light, eye pain, changes in eye sight
  • Persistent or severe muscle pain or weakness, muscle cramps
  • Low red blood cells, bruising.
Infusion-related reactions can sometimes be severe or life-threatening. Signs and symptoms of infusion-related reactions may include:
  • chills or shaking
  • hives
  • flushing
  • shortness of breath or wheezing
  • dizziness
  • feel like passing out
  • fever
  • back pain
  • stomach area (abdomen) pain
Complications, including graft-versus-host-disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with BAVENCIO. Your healthcare provider will monitor you for these complications. Heart problems. When BAVENCIO is used with the medicine axitinib, severe heart problems can happen and can lead to death. Signs and symptoms of heart problems may include:
  • swelling of your stomach area (abdomen), legs, hands, feet, or ankles
  • shortness of breath
  • nausea or vomiting
  • new or worsening chest discomfort, including pain or pressure
  • weight gain
  • pain or discomfort in your arms, back, neck, or jaw
  • breaking out in a cold sweat
  • feeling lightheaded or dizzy
Getting medical treatment right away may help keep these problems from becoming more serious. Your healthcare provider will check you for these problems during your treatment with BAVENCIO. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may also need to delay or completely stop treatment with BAVENCIO if you have severe side effects.
What is BAVENCIO? BAVENCIO is a prescription medicine used to treat:
  • a type of skin cancer called Merkel cell carcinoma (MCC) in adults and children 12 years of age and older. BAVENCIO may be used when your skin cancer has spread.
  • a type of cancer in the bladder or urinary tract called urothelial carcinoma (UC) when it has spread or cannot be removed by surgery (advanced UC). BAVENCIO may be used:
    • as maintenance treatment when your cancer has responded or stabilized after you have received platinum-containing chemotherapy as your first treatment.
    • when you have received platinum-containing chemotherapy, and it did not work or is no longer working.
  • a type of kidney cancer called renal cell carcinoma (RCC). BAVENCIO may be used with the medicine axitinib as your first treatment when your kidney cancer has spread or cannot be removed by surgery (advanced RCC).
It is not known if BAVENCIO is safe and effective in children under the age of 12.
Before you receive BAVENCIO, tell your healthcare provider about all of your medical conditions, including if you:
  • have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus
  • have received an organ transplant
  • have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic)
  • have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome
  • have heart problems or high blood pressure
  • have a high cholesterol level in your blood
  • are pregnant or plan to become pregnant. BAVENCIO can harm your unborn baby.Females who are able to become pregnant:
    • You should use an effective method of birth control during your treatment and for at least 1 month after the last dose of BAVENCIO. Talk to your healthcare provider about birth control methods that you can use during this time.
  • are breastfeeding or plan to breastfeed. It is not known if BAVENCIO passes into your breast milk. Do not breastfeed during treatment and for at least 1 month after the final dose of BAVENCIO.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
How will I receive BAVENCIO?
  • Your healthcare provider will give you BAVENCIO into your vein through an intravenous (IV) line over 60 minutes.
  • BAVENCIO is usually given every 2 weeks.
  • Your healthcare provider will give you medicines before the first 4 infusions and then as needed to help reduce infusion reactions.
  • Your healthcare provider will decide how many treatments you need.
  • Your healthcare provider will do blood tests to check you for certain side effects.
  • If you miss an appointment, call your healthcare provider as soon as possible to reschedule your appointment.
What are the possible side effects of BAVENCIO?BAVENCIO can cause serious side effects, including: The most common side effects of BAVENCIO in people with MCC include:
  • feeling tired
  • muscle and bone pain
  • diarrhea
  • nausea
  • infusion-related reactions including chills, fever, and back pain
  • rash
  • decreased appetite
  • swelling in your hands, feet, or ankles
The most common side effects of BAVENCIO as maintenance treatment in people with UC whose cancer responded or stabilized after platinum-containing chemotherapy as first treatment include:
  • feeling tired
  • muscle and bone pain
  • urinary tract infection
  • rash
The most common side effects of BAVENCIO in people with UC after platinum-containing chemotherapy that did not work, or is no longer working, include:
  • feeling tired
  • infusion-related reactions including chills, fever, back pain, redness, and shortness of breath
  • muscle and bone pain
  • nausea
  • decreased appetite
  • urinary tract infection
The most common side effects of BAVENCIO when given with axitinib in people with RCC include:
  • diarrhea
  • feeling tired
  • high blood pressure
  • muscle and bone pain
  • nausea
  • mouth sores
  • liver problems
  • blisters or rash on the palms of your hands and soles of your feet
  • hoarseness
  • decreased appetite
  • low levels of thyroid hormone
  • rash
  • shortness of breath
  • cough
  • stomach area (abdomen) pain
  • headache
These are not all the possible side effects of BAVENCIO.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
General information about the safe and effective use of BAVENCIO. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. If you would like more information about BAVENCIO, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about BAVENCIO that is written for health professionals.
What are the ingredients in BAVENCIO? Active ingredient: avelumabInactive ingredients: D-mannitol, glacial acetic acid, polysorbate 20, sodium hydroxide, and Water for Injection Manufactured by: EMD Serono, Inc. One Technology Place, Rockland, MA 02370 USA, U.S. License No. 1773.Marketed by: EMD Serono, Inc. and Pfizer Inc., NY, NY 10017 USA.BAVENCIO is a trademark of Merck KGaA, Darmstadt, Germany.For more information, call toll-free 1-844-826-8371 or go to www.bavencio.com.

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