Pharmacist level training presentation was researched and developed at my speciality APPE elective. In the presentation, I discuss 4 oncologic therapeutics that are newly approved. The medications outlines are Kimmtrak, Xpovio, Rubraca, and zalifrelimab. Each of these medications are outline by disease state and full prescribing information.

1. Oncology Therapeutics
Jonathan Strandberg, PharmD Candidate 2023
Specialty APPE Rotation: PFSP
October 14th, 2022

2. Outcomes
Outline specific disease states and indication for four oncologic
therapeutics
Discuss in detail prescribing information for Kimmtrak, Xpovio,
Rubraca, and Zalifrelimab
Review knowledge-based questions regarding discussed
therapeutics.

3. Unresectable or
Metastatic Uveal
Melanoma
Rare malignancy that arises from melanocytes within the uveal tract of the eye,
which includes the iris, ciliary body and choroid
Timing of metastases
• Most patients develop metastatic uveal melanoma within 5-7 years of
treatment to the primary eye tumor
• Despite effective treatment to primary site, the risk of distant metastasis is 50%
Site of Metastases
• Liver (93%)
• Lung (24%)
• Bone (16%)
• Skin/subcutaneous tissue (11%)
• Lymph node and brain metastasis (5-6%)

4. Clinical
Presentation
Majority of the patients are asymptomatic
at diagnosis since most cases are
incidentally diagnosed during routine
imaging
Patients may present with constitutional
symptoms such as fatigue, weight loss and
anorexia
Presence of other symptoms can indicate
disease location (i.e., abdominal pain,
swelling, fullness or back pain (liver))

5. Clinical Factors Affecting Choice of Therapy
Genotype
assessment for
HLA-A*02:01
Tumor burden Rate of growth
Location
Availability of
clinical trials

6. HLA-A*02:01
Positive FDA
Approved Treatment

7. • Kimmtrak (tebentafusp-tebn)
BRAND/GENERIC
• Immunocore Limited
MANUFACTURER
• One single dosed vial containing 100mcg of Kimmtrak in
0.5 mL of sterile, preservative free, clear, colorless or
slightly yellowish solution
SUPPLIED
• Treatment of HLA-A*02:01 positive adult patients with
unresectable or metastatic uveal melanoma
INDICATION

8. Mechanism of Action
• Kimmtrak is a bispecific gp100 peptide-HLA-
A*02:01 directed T cell receptor CD3 T cell engager
that binds to a gp100 peptide on the cell surface of
uveal melanoma tumor cells.
• Kimmtrak binds to uveal melanoma cells and
cytotoxic T cells, forming an immune synapse
• The T cells become active, releasing cytokines to
attract more T cells and lytic granules to contribute
to tumor cell death.

9. Monitoring
Parameters
Genotype testing for HLA-A*02:01 (POSITIVE)
ALT, AST, and total bilirubin; prior to the start of
initiation and during treatment
Fluid Status, vital signs, oxygenation
Pregnancy status
Signs of Cytokine Release Syndrome (CRS)
Skin reactions

10. Kimmtrak
Dosing

11. Special Populations
Pediatric Dosing
• Safety and
efficacy not
established in
pediatric patients
Renal/Hepatic
Impairment
• No specific
recommendations
are available
Pregnancy
• May cause fetal
harm
Lactation
• Infant risk can not
be ruled out.

12. Preparation of
Kimmtrak
Step 1: Prepare the infusion bag, using aseptic technique
• Using a 1 mL syringe withdraw the calculated volume
of Albumin (human) into the syringe and add to 100
mL 0.9% Sodium Chloride injection, USP bag to make a
final Albumin concentration of 250 mcg/mL

13. Preparation of
Kimmtrak Cont.
Step 2: Preparation of Kimmtrak solution for infusion
• Do not shake the Kimmtrak vial
• Using a 1 mL syringe withdraw the required volume of
Kimmtrak 100mcg/0.5 mL as per the dose required (shown on
right) and add to the prepared 100 mL infusion bag
• Discard the single dose vial containing the unused portion of
Kimmtrak in accordance with local requirements. DO NOT
prepare more than one dose from the vial
• Mix the infusion bag by following the same procedure outlines

14. Prior to
Administering
Kimmtrak
• No standard premedication is required
• Ensure the patients are euvolemic prior to initiating the
infusion. Administer IV fluids based on clinical evaluation,
baseline vital signs and volume status.
• For patients on maintenance systemic corticosteroids,
consider adjusting the corticosteroid dose given the risk of
hypotension

15. Administering
Kimmtrak
Upon completion of Kimmtrak infusion, flush the infusion line with
adequate volume of sterile 0.9% sodium chloride injection, USP to
ensure that the entire contents of the infusion bag are administered
DO NOT mix Kimmtrak with drugs other than albumin used during
preparations or administer other drugs through the same IV line
Immediately administer the diluted solution via intravenous infusion
over 15-20 minutes through a dedicated IV line
A sterile, non-pyrogenic, low
protein binding 0.2 micron in-line
filter infusion set should be used
Administer the entire contents of
the Kimmtrak infusion bag

16. Kimmtrak Storage
Store Kimmtrak vials in the original carton refrigerated
at 2℃ to 8℃ and protect from light until time of use
Do not freeze. DO NOT SHAKE
Kimmtrak does not contain a preservative
Kimmtrak is stable for 4 hours if kept at room temperature
If not used immediately, store Kimmtrak in a refrigerator and infuse
within 24 hours from time of preparation
Once removed from refrigerator, do not refrigerate the Kimmtrak
infusion bag again

17. Adverse
Effects
• Common
• Cardiovascular: Edema (45%), Hypotension (39%)
• Dermatologic: Dry skin (31%)
• Gastrointestinal: Abdominal pain (45%), Nausea (49%),
Vomiting (30%)
• Neurological: Headache (31%)
• Other: Fatigue (64%), Fever (76%), Shivering (48%)

18. Adverse Effects Cont.
• Serious
• Dermatological:
Edematous skin (27%),
Erythema (24%), Pruritus
(69%), Rash (83%)
• Hepatic: ALT/SGPT level
raised (52%), Aspartate
aminotransferase serum
level raised (55%)
• Immunologic: Cytokine
release syndrome (89%)

19. Adverse Event
Management

20. Adverse Event Management cont.

21. Adverse Event Management Cont.

22. Adverse Event Management cont.

23. Applicable Patient Counseling
Instruct patients to report
symptoms of cytokine
release syndrome
including hypotension,
chills, nausea, vomiting,
fatigue, or headache
1
Advise women of
reproductive potential to
use effective
contraception during
therapy and for 1 week
after last dose
2
Tell patients to report
symptoms of progressive
or intolerable skin
reactions
3
Inform patients to report
signs of liver toxicity
4

24. PA Clinical
Considerations
Length of Authorization: 6-12 months
• Patient must be >18 years of age;
• Patients must have a documented diagnosis of uveal
melanoma
• Metastatic or unresectable; AND
• HLA-A*02:01 Positive
Initial Criteria
• Patient met initial review criteria; AND
• Documentation of improved clinical response with no signs of
disease progression; AND
• Patient has not experienced any treatment-restricting adverse
effects; AND
• Dosing is appropriate
Continuation of therapy

25. Ordering Kimmtrak(Limited Distribution)

26. Patient assistance
• Kimmtrak connect
• Dedicated nurse case manager that will help identify resources and
services that are available to you.

27. Multiple Myeloma
• Multiple myeloma is characterized by the
neoplastic proliferation of plasma cells
producing a monoclonal immunoglobulin
• The plasma cells proliferate in the bone
marrow and can result in extensive skeletal
destruction with osteolytic lesions,
osteopenia, and/or pathologic fractures

28. Clinical
Presentation
Bone pain with lytic lesions discovered on
routine skeletal films or other imaging
modalities
An increased total serum protein
concentration and/or the presence of a
monoclonal protein in the urine or serum
Systemic signs or symptoms suggestive of
malignancy, such as unexplained anemia
Hypercalcemia, which is either
symptomatic or discovered incidentally

29. Relapsed Refractory Multiple Myeloma
• Cancer that does not improve with therapy or stops responding to it.
• Sometimes, the cancer might initially improve but then becomes resistant to treatment
and starts growing again
• Most people can experience remissions and relapses throughout the course of the disease

30. Relapsed/Refractory
Multiple Myeloma
Management

31. Diffuse Large Cell B
Lymphoma (DLBCL)
• DLBCL is the most common histologic subtype of
non-Hodgkin lymphoma accounting for
approximately 25% of cases.
• DLBCL is a heterogenous group of tumors
consisting of large, transformed B cells with
prominent nucleoli and basophilic cytoplasm, a
diffuse growth pattern and high (>40%)
proliferation factor

32. Clinical
Presentation
Patients with DLBCL typically present with
a rapidly enlarging symptomatic mass,
most usually nodal enlargement in the
neck or abdomen
Systemic “B” symptoms observed in 30%
of patients (fever, weight loss, drenching
night sweats)
Elevated serum lactate dehydrogenases in
over 50% of patients

33. Relapsed/refractory DLBCL
• Nearly 1/3 of patients relapse after achieving a complete response of DLBCL using R-CHOP
and 10% are refractory to initial therapy
• Further Treatment is dependent on if patients are medically fit or unfit
• For patients that are medically unfit (second or later relapse) the goals are to relive
symptoms, prolong survival and control disease, while limiting treatment-related toxicity
• Treatment must be individualized to the patient

34. Relapsed/Refractory
DLBLC & MM FDA
Approved Treatment

35. • Xpovio (Selinexor)
BRAND/GENERIC
• Karyopharm Therapeutics
MANUFACTURER
• 20, 40, 50, 60 mg tablets
SUPPLIED
• Treatment of adult patients with RRMM who have received at
least 4 prior therapies
• Treatment of adult patients with MM, in combination with
bortezomib and dexamethasone in patients who have received at
least 1 prior therapy.
• For adults with RR DLBCL who have received at least two previous
treatments
INDICATION

36. Mechanism of Action
• Xpovio is a reversible nuclear exportin 1 (XPO1)
inhibitor that causes apoptosis of cancer cells by
inhibiting tumor suppressor proteins (TSPs), growth
regulators and mRNA of oncogenic proteins
• XPO1 inhibition by Xpovio leads to accumulation of
TSPs in the nucleus and reductions in several
oncoproteins, such as c-myc and cyclin D1, cell
cycle arrest and apoptosis of cancer cells

37. Monitoring
Parameters
CBC with differential, especially platelets and neutrophils. At baseline and during
use as clinically indicated, with more frequent evaluation during initial 3 months of
use
Sodium levels: At baseline and during use as clinically indicated, with more
frequent evaluation during initial 3 months of use
Body weight: At baseline and during use as clinically indicated, with more frequent
evaluation during initial 3 months of use
Nutritional status: At baseline and during use as clinically indicated, with more
frequent evaluation during initial 3 months of use
Volume status: At baseline and during use as clinically indicated, with more
frequent evaluation during initial 3 months of use
Pregnancy status

38. Xpovio Dosing • Multiple myeloma in combination with bortezomib and
dexamethasone in patients who have received at least 1 prior therapy
• Prophylaxis, maintain adequate fluid and caloric intake throughout
treatment and consider IV hydration in patients at risk of dehydration;
give 5-HT3 antagonist and other anti-nausea agents prior to and
during treatment

39. Xpovio Dosing
Cont.
• Treatment of adults with RRMM who have received at
least 4 prior therapies and whose disease is refractory
to at least two proteasome inhibitor, at least two
immunomodulatory agents and an anti-CD38
monoclonal antibody

40. Xpovio Dosing
Cont.
• DLBCL, relapsed or refractory following at least 2 lines of
systemic therapy
• Prophylaxis, maintain adequate fluid and caloric intake
throughout treatment and consider IV hydration in patients
at risk of dehydration; give 5-HT3 antagonist and other
anti-nausea agents prior to and during treatment

41. Special Population
Pediatric Dosing
• Safety and
effectiveness has
not been
established in
pediatric patients
Pregnancy Category
• Fetal risk cannot
be ruled out
(MDX)
Breast Feeding
• Infant risk cannot
be ruled out
Renal/Hepatic
Impairment
• No specific dosing
recommendations
are provided

42. Preparation
(Administration)
• Swallow tablets whole with water approximately at the
same time everyday; do not break, chew, crush or divide
• Missed or delayed dose: Take the next dose at the next
regularly scheduled time
• Vomited dose: Do not repeat the dose, take the next dose
on the next regularly scheduled day

43. Xpovio Storage
Store at or below 30℃ (86℉) Keep away from heat, moisture, and
direct light

44. Adverse
Effects
• Common
• Gastrointestinal: constipation (25-29%), decrease in
appetite (35-37%), diarrhea (32-44%), nausea (50-
72%), vomiting (21-41%)
• Hematologic: Anemia, all grades (MM, 59%),
Leukopenia (MM, 28%), Neutropenia, all grades (34-
48%), thrombocytopenia, all grades (74-92%)
• Respiratory: dyspnea (10%-24%), Upper respiratory
infection (74-92%)
• Other: Fatigue or asthenia (59-73%)

45. Adverse
Effects Cont.
• Serious
• Cardiovascular: Heart failure (DLBCL, 3%)
• Endocrine metabolic: hyponatremia (39-62%), Weight
loss (26-47%)
• Gastrointestinal: loss of appetite (37%-53%)
• Hematologic: Anemia, grade 3 or higher (MM, 28%),
febrile neutropenia (up to 3%), hemorrhage (10-23%),
Neutropenia, grade 3 or 4 (12-21%),
thrombocytopenia, grade 3 or 4 (43-61%)
• Neurologic: Neurotoxicity (25-30%)
• Ophthalmic: Cataract (DLBCL, 2.7%); (MM, 22%)
• Other: Infectious disease (49-69%), sepsis (6%)

46. Adverse Effect
Management
in MM

47. Adverse Effect
Management
in DLBCL

48. Adverse Effect
Management
Cont.

49. Xpovio Dosage Reduction Steps for
Adverse Effects

50. Applicable
Patient
Counseling
Advise patient to maintain appropriate fluid and caloric
intake during treatment
Warn patients to report symptoms of thrombocytopenia or
anemia
Avoid activities requiring mental alertness or coordination
until drug effects are realized
Avoid pregnancy during therapy and for at least 1 week
after final dose
Report serious side effects
Take 5-HT3 antagonist prophylactic treatment prior and
during therapy**

51. PA Clinical
Considerations:
Multiple
Myeloma
Length of authorization: 12 months
• Diagnosis of RRMM; AND
• Patient has received at least 4 prior therapies; AND
• Disease is refractory to 2 proteasome inhibitors, 2
immunomodulatory agents, and an anti-CD38 monoclonal
antibody; AND
• Used in combo with dexamethasone
Initial criteria (1)
• Diagnosis of MM; AND
• Patient has received at least one prior therapy; AND
• In combo with bortezomib and dexamethasone
Initial criteria (2)
• Patient does not show evidence of progressive disease
Continuation of therapy

52. PA Clinical
Considerations:
DLBCL
Length of authorization: 12 months
• Diagnosis of relapsed or refractory DLBCL;
AND
• Patient has received at least 2 lines of
systemic therapy
Initial criteria
• Patient does not show evidence of
progressive disease
Continuation of therapy

53. Ordering Xpovio (Limited Distribution)

54. Patient Assistance
Program
• KaryForward
• Licensed team of oncology nurses that provides
personalized support for patients and caregivers
• Xpovio Copay Program: Pay as little as $5 for each
prescription.

55. Castration-resistant
Prostate Cancer
• CRPC is defined by disease progression
despite Androgen depletion therapy
• May present as either a continuous rise in
serum prostate-specific antigen levels, the
progression of pre-existing disease, and or
the appearance of new metastases
• Skeletal manifestations are especially
common because prostate cancer has a
strong preference for metastasizing to the
bone

56. Clinical
Presentation
of Advanced
Disease
Weight loss and loss of appetite
Anemia
Bone pain, with or without pathologic fracture
Neurologic deficits from spinal cord compression
Lower extremity pain and edema due to obstruction of
venous and lymphatic tributaries by nodal metastasis

57. Ovarian Cancer, Fallopian
Tube or Primary
Peritoneal Cancer
• Ovarian cancer is the second most common
gynecologic malignancy and most common
cause of gynecologic cancer death
• Most primary ovarian malignancies are
derived from epithelial cells; the remainder
arise from other ovarian cell types
• Patients with ovarian cancer susceptibility
genes (e.g., BRCA gene mutations) are at
highest risk of ovarian cancer

58. Clinical
Presentation
May be either subacute or acute
Presence of pelvic or abdominal pain, bloating
Adnexal mass is discovered incidentally
Acute presentation may present in patients
with advanced disease and includes pleural
effusion or bowel obstruction

59. Approved
Treatment with
Deleterious
BRCA Mutation
Ovarian/
Prostate Cancer

60. •Rubraca (rucaparib)
BRAND/GENERIC
•Clovis Oncology Inc.
MANUFACTURER
•Rubraca is available as 200 mg, 250 mg, 300 mg
SUPPLIED
•Metastatic castration-resistant prostate cancer, with a deleterious
BRCA mutation previously treated with androgen receptor directed
therapy and taxane-based chemotherapy
•Ovarian cancer, fallopian tube or primary peritoneal cancer, deleterious
BRCA mutations after 2 or more previous chemotherapy, treatment
•Ovarian cancer, fallopian tube or primary peritoneal cancer, recurrent
disease after complete or partial response to platinum-based
chemotherapy, maintenance therapy
INDICATION

61. Mechanism of Action
• Rubraca is a poly (ADP-ribose) polymerase inhibitor
that causes DNA damage, apoptosis and cell death,
especially in tumor cell lines with deficiencies in
BRCA 1 & 2

62. Monitoring
Parameters
Presence of deleterious BRCA mutation prior to
initiation
CBC prior to initiation of therapy and monthly
thereafter; if prolonged hematological toxicities
occur, monitor CBC weekly until recovery
Tumor response may indicate efficacy

63. Dosing
Rubraca
Patient receiving Rubraca for mCRPC must receive a GnRH analog or have
had a bilateral orchiectomy

64. Special Populations
Pediatric Dosing
• Safety and
effectiveness have
not been established
in pediatric patients.
Hepatic/ Renal
(moderate-severe
impairment)
• This population has
not been studied
Pregnancy Category
• Fetal. Risk cannot be
ruled out (MDX)
Lactation
• Infant risk cannot be
ruled out

65. Preparation
(Administration)
• Give with or without food
• Missed or vomited: Do not take an extra dose; take the
next dose at the regular time

66. Rubraca Storage
STORE AT ROOM TEMPERATURE
20℃ TO 25℃ (68℉ TO 77℉)
STORE MEDICATION IN A SAFE
LOCATION; AWAY FROM CHILDREN

67. Adverse
Effects
• Common
• Dermatologic: Rash (13-43%)
• Gastrointestinal: Abdominal pain (32-46%),
constipation (27-40%), decrease in appetite (23-39%),
diarrhea (20-34%), nausea (52-77%), stomatitis (28%),
taste sense altered (39-40%), vomiting (22-46%)
• Hematologic: Anemia, grade 1-4 (39-44%),
Neutropenia, grade 1-4 (15-20%), thrombocytopenia,
grade 1-4 (21-29%)
• Hepatic: ALT/SGPT level raised, increased aspartate
transaminase level
• Neurologic: Asthenia
• Respiratory: dyspnea (up to 21%), Nasopharyngitis,
upper respiratory infection
• Other: Fatigue

68. Adverse
Effects Cont.
• Serious
• Hematologic: Anemia, grade 3 or 4 (21-25%),
Myelodysplastic syndrome, Myeloid leukemia,
neutropenia, grade 3 or 4 (8%), thrombocytopenia,
grade 3 or 4 (5-10%)
• Immunologic: Hypersensitivity reaction (less than
20%), sepsis (less than 20%)
• Respiratory: Pneumonia (less than 20%)

69. Adverse Event
Management
• Adverse events: consider interruption or dosage reduction
• Do not initiate Rubraca until recovery to grade 1 or less from hematological
toxicity caused by previous chemotherapy
• For hematologic toxicity lasting more than 4 weeks, interrupt therapy or dosage
reduction
• If levels do not recover to grade 1 or less refer to hematologist and
discontinue Rubraca

70. Drug
Interactions
Co-administration of Rubraca can increase
systemic exposure of CYP1A2, CYP3A4,
CYP2C9, CYP2C19 substrates, which may
increase the risk of toxicities of these drugs.
• Adjust dosage of above substrates, if clinically indicated
Warfarin-Rubraca: Concurrent use may
result in increased warfarin exposure

71. Applicable Patient Counseling
Advise patients to
report symptoms of
myelodysplastic
syndrome or acute
myeloid leukemia
1
Tell patients to use
sunscreen, wear
protective clothing and
avoid tanning beds due
to potential for
photosensitivity
2
Recommend female
patient avoid pregnancy
during therapy and for 6
months after the last
dose
3
Use effective
contraception during
therapy and for 3
months after the last
dose
4

72. Managing Side Effects
Weakness/Fatigue
• Balancing your daily
routine with both
rest and physical
activity. Try light
exercise every day,
with plenty of short
naps or breaks
Nausea/Vomiting
• Eating small,
frequent meals or
all-liquid diet
• Choosing foods that
are easy on the
stomach (dry
toast/crackers)
• Antiemetics or
antinausea
medication
Decreased Appetite
• Eating foods that are
high in calories and
easy to eat
• Eat 5 or 6 small
meals or snack
instead of 3 big
meals
• Having liquid meals
Diarrhea
• Eating foods high in
sodium and
potassium
• Drinking 8-12 cups
of clear liquid each
day
• Taking OTC
antidiarrheals

73. PA Clinical
Considerations:
Ovarian Cancer
Length of authorization: 12 months
• Individual is >18 years of age; AND
• Individual has a BRCA-mutation (germline or somatic)
confirmed; AND
• Individual has progressed on two or more prior lines of
chemotherapy
Initial criteria (1)
• Individual is >18 of age; AND
• Individual is in complete or partial response after at lease two
platinum-based chemotherapy
Initial criteria (2)
• Patient does not show evidence of progressive disease
Continuation of therapy

74. PA Clinical
Considerations:
Prostate
Cancer
Length of authorization: 12 months
• Diagnosis of mCRPC; AND
• Cancer has a deleterious BRCA mutation; AND
• Individual is concurrently using a GnRH analog or
has had a bilateral orchiectomy; AND
• Individual has been previously treated with at least
one androgen receptor-directed therapy and taxane
based chemotherapy
Initial criteria
• Patient does not show evidence of progressive
disease
Continuation of therapy

75. Ordering Rubraca (Limited Network)

76. Patient Assistance Programs
• Rubraca Connections $0 Co-pay program with private or commercial insurance
• Clovis Cares: Dedicated nurse case manager to make resources and services available

77. Cervical Cancer
• Cervical Cancer is cancer that starts in the cervix, the
narrow opening into the uterus from the vagina
• The ”transformation zone” (T-zone) is where the
ectocervix and endocervix meet
• This is the most likely the location for abnormal
or precancerous cells to develop
• Most cervical cancer (80-90%) are squamous cell
cancers
• Metastatic disease will develop in 15-61% of women
with cervical cancer, usually within the first two years
of completing treatment
• In most cases, metastatic cervical cancer is not curable

78. Clinical
Presentation
Vaginal symptoms (i.e., discharge
bleeding, dyspareunia, or pain)
On pelvic exam, a mass or nodularity at
the vaginal cuff, which may extend to the
pelvic side wall
Patients with metastatic cervical cancer
usually present with either no symptoms
or nonspecific complaints (i.e., fatigue,
nausea, or weight loss)

79. Current Guidelines
• For patients with recurrent and/or metastatic cervical cancer, treatments remain
suboptimal, particularly for those who progress after first line chemotherapy doublet plus
bevacizumab
• To date the only immunotherapeutic indicated for use is the PD-1 antibody
pembrolizumab
• Dual targeted immunotherapy is a clinically validated strategy for optimizing antitumor
activity over anti-PD1 monotherapy, typically involving the addition of antibodies directed
to CTLA-4
• The most widely used anti-PD1 and CTLA-4 combination is nivolumab plus ipilimumab

80. Zalifrelimab in
Cervical Cancer

81. • Zalifrelimab (AGEN 1884)
BRAND/GENERIC
• Agenus Inc
MANUFACTURER
• No available Information
SUPPLIED
• Checkpoint inhibitor emerging as promising
investigational agent for the treatment of
advanced cervical cancer
INDICATION

82. Mechanism of Action
• A recombinant human monoclonal antibody
directed against the human T-cell receptor CTLA-4,
with immune checkpoint inhibitor and
antineoplastic activities.
• Binds to CTLA-4 expressed on T-cells and inhibits
the CTLA-4 mediated downregulation of T cell
activity
• This leads to cytotoxic T-lymphocyte (TCL)
mediated immune response against cancer cells

83. Dual PD-1 and CTLA-4 Checkpoint
Blockade Using Balstilimab and
Zalifrelimab Combination as Second-
Line Treatment for Advanced Cervical
Cancer: An Open-Label Phase II Study

84. Requirements Prior to Dosing
Requirements
• Age >18 years of age
• ECOG performance status
score of 0 or 1
• Adequate hematologic, renal,
and hepatic function
Exclusions
• Prior immune checkpoint
targeted therapy
• Known hypersensitivity to
humanized monoclonal
antibodies
• >1 systemic treatment regimen
for recurrent/metastatic
cervical cancer

85. Dosing Zalifrelimab/Balstilimab
• Patients received 3mg/kg Balstilimab once every two weeks plus 1 mg/kg Zalifrelimab
once every six weeks over a 6-week cycle, each of which included three doses of biweekly
Balstilimab and one dose of Zalifrelimab
• Balstilimab was delivery intravenously on days 1,15,29 of each cycle; Zalifrelimab was
administered intravenously after completion of Balstilimab infusion on day 1 only

86. Monitoring
Parameters
Patients were monitored for infusion reactions for at least 30
minutes after dosing
Adverse effects were monitored continuously from the time
of the first study dose until at least 30 days after the last
dose of study drug
Monitor and evaluate tumor response
Treatment was continued until disease progression,
development of unacceptable toxicity or investigator and/or
patient decision and permitted for up to 24 months

87. Adverse
Effects
• Common treatment-related of any grade (majority being
grade 1 or 2)
• Hypothyroidism (16.8%)
• Diarrhea (14.2%)
• Fatigue (11.6%)
• Nausea (9%)

88. Adverse
Effects Cont.
• Treatment related adverse effects leading to dose
interruptions or discontinuations
• Occurred in 19 (12.3%) and 12(7.7%) patients
• Elevations in AST (n=4) or ALT levels (n=3) were the
leading cause in dose interruptions
• Diarrhea (n=3) was the leading cause of treatment
discontinuation
• Serious adverse effects
• Experienced by a total of 16 patients (10.3%)
• Immune-mediated enterocolitis being the most
common (n=3)
• Three deaths were related to the treatment (involved
pneumonitis, immune-mediated nephritis, diabetes
mellitus)

89. Promise for Approval
• Balstilimab plus Zalifrelimab combination produced durable responses as second-line
treatment
• The primary outcome of interest (objective response rate) was observed in 25.6% of
patients, with disease control reported in 52%
• The median response duration was not reached, with 64.2% of responses ongoing at 12
months
• Further investigation of combination in this setting is continuing

90. Zalifrelimab Pipeline
**Urogen has an exclusive license to develop and commercialize Zalifrelimab for the treatment of urinary tract cancers
**Nelum is conducting a clinical trial combining Zalifrelimab with NLM-001 in patient with advanced pancreatic cancer

91. Which of the
following is true
regarding Kimmtrak
storage?
A) Before infusing Kimmtrak into the saline
bag, you must shake the vial
B) It is acceptable to freeze the Kimmtrak vial
C) Kimmtrak is stable for 12 hours if kept at
room temperature.
D) If not used immediately, store Kimmtrak in
refrigerator and infuse within 24 hours.

92. What adverse
reaction is most
closely associated
with Kimmtrak?
A) Cytokine release syndrome
B) Anemia
C) Upper respiratory tract infection
D) Hypothyroidism

93. Patients taking
Rubraca for
mCRPC, must also
A) Be taking a GnRH agonist such as Lupron
B) Be taking a G-CSF medication such as
Neupogen
C) Have had a bilateral orchiectomy
D) Both A or C are correct.

94. If a patient is
experiencing level 3
elevated liver
enzymes. What is
the next step?
A)Permanently discontinue Kimmtrak
B) Withhold Kimmtrak until graded level 2
and resume at same does level
C) Resume Kimmtrak at grade level 1 and
escalate the dose.
D) Administer IV corticosteroids if no
improvement is seen in 24 hours.

95. What prophylactic
treatment is
necessary for
Xpovio?
A) Diphenhydramine
B) Omeprazole
C) Ondansetron
D) Ibuprofen

96. What is the correct
dosing for
Zalifrelimab/Balstilimab
combination?
A) Zalifrelimab 3 mg/kg on days 1, 15, 29,
and Balstilimab 1 mg/kg on day 1
B) Zalifrelimab 3 mg/kg on day 1 and
Balstilimab 1 mg/kg on days 1, 15, 29
C) Zalifrelimab 1 mg/ kg on day 1 and
Balstilimab 3 mg/kg on days 1, 15, 29
D) Zalifrelimab 1 mg/kg on days 1, 15, 29 and
Balstilimab 3 mg/kg on day 1

97. Which of the
following is
applicable patient
counseling for
Xpovio?
A) Avoid activities requiring mental alertness
or coordination until drug effects are
realized.
B) Tell patients to report symptoms of
progressive or intolerable skin reductions
C) Avoid pregnancy during therapy and for at
least 3 months after last dose
D) Tell patients to report signs and symptoms
of stroke or MI

98. Patients JS has been recently
treated with chemotherapy. He
walks into the clinic
complaining of night sweats,
fever, enlarged nodes on neck.
Patient JS is classified as
medically unfit. Which
Oncologic product could be
used?
A) Xpovio
B) Kimmtrak
C) Zalifrelimab
D) Rubraca

99. References
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100. References Cont.
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• Immunocore Ltd. (n.d.). KIMMTRAK® (tebentafusp-tebn) - Official Physician Website | KIMMTRAK (tebentafusp-tebn). Retrieved September 24, 2022,
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101. References Cont.
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102. References Cont.
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