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ELAHERE STUDY SAFETY PROFILE

Adverse events in ≥10% of patients who received ELAHERE in MIRASOL

Adverse event

ELAHERE
(n=218)

Standard chemotherapy
(n=207)

|

  All Grades (%) Grades 3-4 (%) All Grades (%) Grades 3-4 (%)
Abdominal paina 34 3 23 2
Diarrhea 29 1 17 0.5
Constipation 27 0 19 1
Nausea 27 2 29 2
Vomiting 18 3 18 1

  All Grades (%) Grades 3-4 (%) All Grades (%) Grades 3-4 (%)
Blurred visionb 45 9 3 0
Keratopathyc 37 11 0 0
Dry eyed 29 3 5 0
Photophobia 18 0.5 0.5 0
Cataracte 16 3 0.5 0

  All Grades (%) Grades 3-4 (%) All Grades (%) Grades 3-4 (%)
Fatiguef 47 3 41 7

  All Grades (%) Grades 3-4 (%) All Grades (%) Grades 3-4 (%)
Peripheral neuropathyg 37 4 23 4
Headache 14 0 10 0

  All Grades (%) Grades 3-4 (%) All Grades (%) Grades 3-4 (%)
Musculoskeletal painh 31 1 21 2

  All Grades (%) Grades 3-4 (%) All Grades (%) Grades 3-4 (%)
Decreased appetite 18 1 14 1

  All Grades (%) Grades 3-4 (%) All Grades (%) Grades 3-4 (%)
Pneumonitisi 10 0.5 0.5 0

  All Grades (%) Grades 3-4 (%) All Grades (%) Grades 3-4 (%)
Neutropenia 11 0.9 29 17
Anemia 10 0.9 34 10

aAbdominal pain includes abdominal pain, abdominal pain upper, abdominal pain lower, and abdominal discomfort.
bBlurred vision includes vision blurred, vitreous floaters, visual acuity reduced, diplopia, accommodation disorder, and visual impairment.
cKeratopathy includes corneal disorder, corneal epithelial microcysts, keratitis, keratopathy, corneal deposits, punctate keratitis, and corneal opacity.
dDry eye includes dry eye and lacrimation increased.
eCataract includes cataract and cataract nuclear.
fFatigue includes fatigue and asthenia.
gPeripheral neuropathy includes neuropathy peripheral, peripheral sensory neuropathy, peripheral motor neuropathy, paresthesia, hypoesthesia, polyneuropathy, neurotoxicity, and peripheral sensorimotor neuropathy.
hMusculoskeletal pain includes back pain, myalgia, neck pain, arthralgia, musculoskeletal pain, non-cardiac chest pain, bone pain, pain in extremity, musculoskeletal stiffness, musculoskeletal chest pain, and musculoskeletal discomfort.
iPneumonitis includes pneumonitis, interstitial lung disease, respiratory failure, and organizing pneumonia.

Additional MIRASOL study AE information

  ELAHERE
(n=218)
1,2
Standard chemotherapy
(n=207)
2
Grade ≥3 AEs (%) 42
(n=91)
54
(n=112)
Serious AEs (%) 24
(n=52)
33
(n=68)
Discontinuations due to AEs (%) 9
(n=20)
16
(n=33)
Common reasons for discontinuation (≥1%) Pneumonitis (2%), blurred vision (1%), and peripheral neuropathy (1%) Peripheral neuropathy (2%),
thrombocytopenia (1%), and fatigue (1%)
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The most common (≥2%) serious AEs were intestinal obstruction (5%), abdominal pain (3%), and pleural effusion (3%). Fatal AEs occurred in 3% of patients, including intestinal obstruction, dyspnea in the setting of subileus, neutropenic sepsis, cardiopulmonary failure, respiratory failure, ischemic stroke, and pulmonary embolus1

Infusion Bag Icon

Dosage delays of ELAHERE due to an AE occurred in 54% of patients treated with ELAHERE. AEs which required dosage delays in ≥3% of patients included1:

  • Blurred vision (22%)
  • Keratopathy (19%)
  • Dry eye (7%)
  • Neutropenia (6%)
  • Pneumonitis (6%)
  • Photophobia (5%)
  • Cataract (4%)
  • Peripheral neuropathy (4%)
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Dose reductions of ELAHERE due to an AE occurred in 34% of patients. AEs which required dose reductions in ≥3% of patients included1:

  • Blurred vision (14%)
  • Keratopathy (10%)
  • Peripheral neuropathy (6%)
  • Dry eye (5%)
Serious Icon

Clinically relevant AEs that occurred in <10% of patients who received ELAHERE in the MIRASOL study included infusion-related reactions/hypersensitivity (8%)1

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1% of patients treated with ELAHERE reported alopecia (Grade 1) vs 14% of patients treated with standard chemotherapy (7% Grade 1 and 7% Grade 2)3

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In the MIRASOL study, the median duration of ELAHERE treatment was 5 months (range: 0.69 to 27.4)1

Ocular events with ELAHERE from MIRASOL (n=218)2,4*

Ocular events were mostly Grade 1 or 22,4

  • 56% of patients treated with ELAHERE had an ocular AE (n=122); of those who had an ocular AE, 14% were Grade ≥3 (n=30)4
  • Of the patients treated with ELAHERE who had an ocular event (n=122), 51% had complete resolution and 42% had partial improvement. Of the remaining 7% who had no documented improvement, 5% were at Grade 1 and 2% were at Grade 23,4
  • 1.8% of patients treated with ELAHERE discontinued due to ocular-related events2
  • Median time to onset of first ocular AE was 5.4 weeks (range: 0.1 to 68.6)2

No corneal ulcerations or perforations have been reported2

*Data cutoff was March 6, 2023.2
Partial improvement was defined as improvement by ≥1 grade from the worst grade at last follow-up.4

Laboratory abnormalities in MIRASOL1

Select laboratory abnormalities ≥10% for all grades in patients who received ELAHERE in MIRASOL

Laboratory abnormality

ELAHERE
(n=218)

Standard chemotherapy
(n=207)

|

  All Grades (%) Grades 3-4 (%) All Grades (%) Grades 3-4 (%)
Increased AST 57 0 14 0
Increased ALT 38 1 15 1
Increased alkaline phosphatase 30 1 13 1

  All Grades (%) Grades 3-4 (%) All Grades (%) Grades 3-4 (%)
Decreased albumin 21 1 27 2
Decreased magnesium 21 1 29 2
Decreased sodium 16 0 18 0
Decreased potassium 15 1 11 1
Increased calcium 12 0 5 0
Decreased bicarbonate 11 0 11 0
Increased creatinine 10 0 11 0

  All Grades (%) Grades 3-4 (%) All Grades (%) Grades 3-4 (%)
Decreased lymphocytes 27 3 42 11
Decreased leukocytes 23 1 53 10
Decreased neutrophils 22 1 45 17
Decreased hemoglobin 18 1 63 8
Decreased platelets 17 1 20 5

aThe denominator used to calculate the rate varied from 63 to 214 (ELAHERE); 63 to 194 (IC chemo) based on the number of patients with a baseline value and at least one posttreatment value.

Adverse events reported in ≥10% of patients receiving ELAHERE in SORAYA1,3

Adverse event
(N=106)

|

  All Grades (%) Grade 3 (%) Grade 4 (%)
Blurred Visiona 50 6.6 0
Keratopathyb 37 8.5 0.9
Dry eyec 27 1.9 0
Cataract 18 2.8 0
Photophobia 17 0 0
Eye paind 10 0 0

  All Grades (%) Grade 3 (%) Grade 4 (%)
Fatiguee 49 2.8 0

  All Grades (%) Grade 3 (%) Grade 4 (%)
Nausea 40 0 0
Abdominal painf 36 6.6 0
Diarrhea 31 2.8 0
Constipation 30 0.9 0
Vomiting 19 0 0
Abdominal distension 11 0 0

  All Grades (%) Grade 3 (%) Grade 4 (%)
Peripheral neuropathyg 33 1.9 0

  All Grades (%) Grade 3 (%) Grade 4 (%)
Decreased appetite 18 0.9 0

  All Grades (%) Grade 3 (%) Grade 4 (%)
Arthralgia 17 0 0
Myalgia 10 0 0

  All Grades (%) Grade 3 (%) Grade 4 (%)
Dyspneah 12 0 0

aBlurred vision includes vision blurred, vitreous floaters, visual acuity reduced, diplopia, presbyopia, accommodation disorder, visual impairment, and refraction disorder.
bKeratopathy includes corneal disorder, corneal epithelial microcysts, corneal epithelial defect, keratitis, keratopathy, corneal deposits, and punctate keratitis.
cDry eye includes dry eye and lacrimation increased.
dEye pain includes eye pain and ocular discomfort.
eFatigue includes fatigue and asthenia.
fAbdominal pain includes abdominal pain, abdominal pain upper, abdominal pain lower, abdominal discomfort.
gPeripheral neuropathy includes neuropathy peripheral, peripheral sensory neuropathy, peripheral motor neuropathy, paresthesia, hypoesthesia, polyneuropathy, and neurotoxicity.
hDyspnea includes dyspnea and exertional dyspnea.

One patient reported Grade 1 alopecia after treatment with ELAHERE in the SORAYA study3‡

Clinically Relevant Icon

Clinically relevant AEs occurring in <10% of patients who received ELAHERE in SORAYA included1:

  • Infusion-related reactions/hypersensitivity (9%)
  • Pneumonitis (8%)
  • Uveitis (1%)
Serious Icon

Serious AEs occurred in 31% of patients. The most common (≥2%) serious AEs were1:

  • Intestinal obstruction (8%)
  • Ascites (4%)
  • Infection (3%)
  • Pleural effusion (3%)

Fatal AEs occurred in 2% of patients, including small intestinal obstruction (1%) and pneumonitis (1%)1

Permanent Discontinuation Icon

Permanent discontinuation due to AEs occurred in 11% of patients1

  • The most common (≥2%) AEs leading to permanent discontinuation were intestinal obstruction (2%) and thrombocytopenia (2%)
  • One patient (0.9%) permanently discontinued ELAHERE due to visual impairment (unilateral decrease to BCVA ≤20/200 that resolved to baseline after discontinuation)
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Dosage delays of ELAHERE due to an AE occurred in 39% of patients1

AEs which required dosage delays in ≥3% of patients included:

  • Blurred vision (15%)
  • Keratopathy (11%)
  • Neutropenia (6%)
  • Dry eye (5%)
  • Cataracts (3%)
  • Increased gamma-glutamyltransferase (3%)
Down Arrow Icon

Dose reductions of ELAHERE due to an AE occurred in 20% of patients1

  • AEs which required dose reductions in ≥3% of patients included blurred vision (9%) and keratopathy (7%)
Calendar icon

The median duration of treatment was 4.2 months (range: 0.7 to 13.3)1

One additional patient entered the study with Grade 1 alopecia. Alopecia was not a result of ELAHERE and grade did not change during treatment.2

Laboratory abnormalities in SORAYA1

Select laboratory abnormalities ≥10% for all grades or ≥2% for Grades 3-4 in patients who received ELAHERE

Laboratory abnormality

ELAHEREa

|

  All Grades (%) Grades 3-4 (%)
Increased AST 50 2
Increased ALT 39 2
Increased alkaline phosphatase 30 1

  All Grades (%) Grades 3-4 (%)
Decreased lymphocytes 35 7
Decreased leukocytes 26 1
Decreased neutrophils 26 3
Decreased hemoglobin 25 3
Decreased platelets 18 2

  All Grades (%) Grades 3-4 (%)
Decreased albumin 31 1
Decreased magnesium 27 2
Increased creatinine 16 0
Decreased potassium 15 4

aThe denominator used to calculate the rate varied from 98 to 101 based on the number of patients with a baseline value and at least one posttreatment value.

Find out how ELAHERE is dosed and administered

Learn About Dosing

How to Test for FRα

Testing for FRα is carried out at labs that have been validated to perform the VENTANA FOLR1 IHC assay.

How to Order ELAHERE

Please contact your participating specialty distributor or specialty pharmacy partners listed in the ELAHERE Ordering Information Sheet.

AE=adverse event; ALT=alanine aminotransferase; AST=aspartate aminotransferase; BCVA=best corrected visual acuity; FOLR1=folate receptor 1; FRα=folate receptor alpha; IC=investigator’s choice; IHC=immunohistochemistry.

IMPORTANT SAFETY INFORMATION

WARNING: OCULAR TOXICITY

  • ELAHERE can cause severe ocular toxicities, including visual impairment, keratopathy, dry eye, photophobia, eye pain, and uveitis.
  • Conduct an ophthalmic exam including visual acuity and slit lamp exam prior to initiation of ELAHERE, every other cycle for the first 8 cycles, and as clinically indicated.
  • Administer prophylactic artificial tears and ophthalmic topical steroids.
  • Withhold ELAHERE for ocular toxicities until improvement and resume at the same or reduced dose.
  • Discontinue ELAHERE for Grade 4 ocular toxicities.

WARNINGS and PRECAUTIONS

Ocular Disorders

ELAHERE can cause severe ocular adverse reactions, including visual impairment, keratopathy (corneal disorders), dry eye, photophobia, eye pain, and uveitis.

Ocular adverse reactions occurred in 59% of patients with ovarian cancer treated with ELAHERE. Eleven percent (11%) of patients experienced Grade 3 ocular adverse reactions, including blurred vision, keratopathy (corneal disorders), dry eye, cataract, photophobia, and eye pain; two patients (0.3%) experienced Grade 4 events (keratopathy and cataract). The most common (≥5%) ocular adverse reactions were blurred vision (48%), keratopathy (36%), dry eye (27%), cataract (16%), photophobia (14%), and eye pain (10%).

The median time to onset for first ocular adverse reaction was 5.1 weeks (range: 0.1 to 68.6). Of the patients who experienced ocular events, 53% had complete resolution; 38% had partial improvement (defined as a decrease in severity by one or more grades from the worst grade at last follow up). Ocular adverse reactions led to permanent discontinuation of ELAHERE in 1% of patients.

Premedication and use of lubricating and ophthalmic topical steroid eye drops during treatment with ELAHERE are recommended. Advise patients to avoid use of contact lenses during treatment with ELAHERE unless directed by a healthcare provider.

Refer patients to an eye care professional for an ophthalmic exam including visual acuity and slit lamp exam prior to treatment initiation, every other cycle for the first 8 cycles, and as clinically indicated. Promptly refer patients to an eye care professional for any new or worsening ocular signs and symptoms.

Monitor for ocular toxicity and withhold, reduce, or permanently discontinue ELAHERE based on severity and persistence of ocular adverse reactions.

Pneumonitis

Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ELAHERE.

Pneumonitis occurred in 10% of patients treated with ELAHERE, including 1% with Grade 3 events and 1 patient (0.1%) with a Grade 4 event. One patient (0.1%) died due to respiratory failure in the setting of pneumonitis and lung metastases. One patient (0.1%) died due to respiratory failure of unknown etiology. Pneumonitis led to permanent discontinuation of ELAHERE in 3% of patients.

Monitor patients for pulmonary signs and symptoms of pneumonitis, which may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams. Infectious, neoplastic, and other causes for such symptoms should be excluded through appropriate investigations. Withhold ELAHERE for patients who develop persistent or recurrent Grade 2 pneumonitis until symptoms resolve to ≤ Grade 1 and consider dose reduction. Permanently discontinue ELAHERE in all patients with Grade 3 or 4 pneumonitis. Patients who are asymptomatic may continue dosing of ELAHERE with close monitoring.

Peripheral Neuropathy (PN)

Peripheral neuropathy occurred in 36% of patients with ovarian cancer treated with ELAHERE across clinical trials; 3% of patients experienced Grade 3 peripheral neuropathy. Peripheral neuropathy adverse reactions included peripheral neuropathy (20%), peripheral sensory neuropathy (9%), paraesthesia (6%), neurotoxicity (3%), hypoaesthesia (1%), peripheral motor neuropathy (0.9%), polyneuropathy (0.3%), and peripheral sensorimotor neuropathy (0.1%). Monitor patients for signs and symptoms of neuropathy, such as paresthesia, tingling or a burning sensation, neuropathic pain, muscle weakness, or dysesthesia. For patients experiencing new or worsening PN, withhold dosage, dose reduce, or permanently discontinue ELAHERE based on the severity of PN.

Embryo-Fetal Toxicity

Based on its mechanism of action, ELAHERE can cause embryo-fetal harm when administered to a pregnant woman because it contains a genotoxic compound (DM4) and affects actively dividing cells.

Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ELAHERE and for 7 months after the last dose.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions, including lab abnormalities, were increased aspartate aminotransferase, fatigue, increased alanine aminotransferase, blurred vision, nausea, increased alkaline phosphatase, diarrhea, abdominal pain, keratopathy, peripheral neuropathy, musculoskeletal pain, decreased lymphocytes, decreased platelets, decreased magnesium, decreased hemoglobin, dry eye, constipation, decreased leukocytes, vomiting, decreased albumin, decreased appetite, and decreased neutrophils.

DRUG INTERACTIONS

DM4 is a CYP3A4 substrate. Closely monitor patients for adverse reactions with ELAHERE when used concomitantly with strong CYP3A4 inhibitors.

USE IN SPECIAL POPULATIONS

Lactation

Advise women not to breastfeed during treatment with ELAHERE and for 1 month after the last dose.

Hepatic Impairment

Avoid use of ELAHERE in patients with moderate or severe hepatic impairment (total bilirubin >1.5 ULN).

IMPORTANT SAFETY INFORMATION

WARNING: OCULAR TOXICITY

  • ELAHERE can cause severe ocular toxicities, including visual impairment, keratopathy, dry eye, photophobia, eye pain, and uveitis.
  • Conduct an ophthalmic exam including visual acuity and slit lamp exam prior to initiation of ELAHERE, every other cycle for the first 8 cycles, and as clinically indicated.
  • Administer prophylactic artificial tears and ophthalmic topical steroids.
  • Withhold ELAHERE for ocular toxicities until improvement and resume at the same or reduced dose.
  • Discontinue ELAHERE for Grade 4 ocular toxicities.

WARNINGS and PRECAUTIONS

Ocular Disorders

ELAHERE can cause severe ocular adverse reactions, including visual impairment, keratopathy (corneal disorders), dry eye, photophobia, eye pain, and uveitis.

Ocular adverse reactions occurred in 59% of patients with ovarian cancer treated with ELAHERE. Eleven percent (11%) of patients experienced Grade 3 ocular adverse reactions, including blurred vision, keratopathy (corneal disorders), dry eye, cataract, photophobia, and eye pain; two patients (0.3%) experienced Grade 4 events (keratopathy and cataract). The most common (≥5%) ocular adverse reactions were blurred vision (48%), keratopathy (36%), dry eye (27%), cataract (16%), photophobia (14%), and eye pain (10%).

The median time to onset for first ocular adverse reaction was 5.1 weeks (range: 0.1 to 68.6). Of the patients who experienced ocular events, 53% had complete resolution; 38% had partial improvement (defined as a decrease in severity by one or more grades from the worst grade at last follow up). Ocular adverse reactions led to permanent discontinuation of ELAHERE in 1% of patients.

Premedication and use of lubricating and ophthalmic topical steroid eye drops during treatment with ELAHERE are recommended. Advise patients to avoid use of contact lenses during treatment with ELAHERE unless directed by a healthcare provider.

Refer patients to an eye care professional for an ophthalmic exam including visual acuity and slit lamp exam prior to treatment initiation, every other cycle for the first 8 cycles, and as clinically indicated. Promptly refer patients to an eye care professional for any new or worsening ocular signs and symptoms.

Monitor for ocular toxicity and withhold, reduce, or permanently discontinue ELAHERE based on severity and persistence of ocular adverse reactions.

Pneumonitis

Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ELAHERE.

Pneumonitis occurred in 10% of patients treated with ELAHERE, including 1% with Grade 3 events and 1 patient (0.1%) with a Grade 4 event. One patient (0.1%) died due to respiratory failure in the setting of pneumonitis and lung metastases. One patient (0.1%) died due to respiratory failure of unknown etiology. Pneumonitis led to permanent discontinuation of ELAHERE in 3% of patients.

Monitor patients for pulmonary signs and symptoms of pneumonitis, which may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams. Infectious, neoplastic, and other causes for such symptoms should be excluded through appropriate investigations. Withhold ELAHERE for patients who develop persistent or recurrent Grade 2 pneumonitis until symptoms resolve to ≤ Grade 1 and consider dose reduction. Permanently discontinue ELAHERE in all patients with Grade 3 or 4 pneumonitis. Patients who are asymptomatic may continue dosing of ELAHERE with close monitoring.

Peripheral Neuropathy (PN)

Peripheral neuropathy occurred in 36% of patients with ovarian cancer treated with ELAHERE across clinical trials; 3% of patients experienced Grade 3 peripheral neuropathy. Peripheral neuropathy adverse reactions included peripheral neuropathy (20%), peripheral sensory neuropathy (9%), paraesthesia (6%), neurotoxicity (3%), hypoaesthesia (1%), peripheral motor neuropathy (0.9%), polyneuropathy (0.3%), and peripheral sensorimotor neuropathy (0.1%). Monitor patients for signs and symptoms of neuropathy, such as paresthesia, tingling or a burning sensation, neuropathic pain, muscle weakness, or dysesthesia. For patients experiencing new or worsening PN, withhold dosage, dose reduce, or permanently discontinue ELAHERE based on the severity of PN.

Embryo-Fetal Toxicity

Based on its mechanism of action, ELAHERE can cause embryo-fetal harm when administered to a pregnant woman because it contains a genotoxic compound (DM4) and affects actively dividing cells.

Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ELAHERE and for 7 months after the last dose.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions, including lab abnormalities, were increased aspartate aminotransferase, fatigue, increased alanine aminotransferase, blurred vision, nausea, increased alkaline phosphatase, diarrhea, abdominal pain, keratopathy, peripheral neuropathy, musculoskeletal pain, decreased lymphocytes, decreased platelets, decreased magnesium, decreased hemoglobin, dry eye, constipation, decreased leukocytes, vomiting, decreased albumin, decreased appetite, and decreased neutrophils.

DRUG INTERACTIONS

DM4 is a CYP3A4 substrate. Closely monitor patients for adverse reactions with ELAHERE when used concomitantly with strong CYP3A4 inhibitors.

USE IN SPECIAL POPULATIONS

Lactation

Advise women not to breastfeed during treatment with ELAHERE and for 1 month after the last dose.

Hepatic Impairment

Avoid use of ELAHERE in patients with moderate or severe hepatic impairment (total bilirubin >1.5 ULN).

INDICATION

ELAHERE is indicated for the treatment of adult patients with folate receptor-alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Select patients for therapy based on an FDA-approved test.

Please see Full Prescribing Information, including Boxed WARNING.

References

  1. ELAHERE. Package insert. ImmunoGen, Inc.; 2024.
  2. Moore KN, Angelergues A, Konecny GE, et al. Mirvetuximab soravtansine in FRα-positive, platinum-resistant ovarian cancer. N Engl J Med. 2023;389:2162–2174.
  3. Data on file. ImmunoGen, Inc. Waltham, MA.
  4. Moore KN, Angelergues A, Konecny GE, et al. Mirvetuximab soravtansine in FRα-positive, platinum-resistant ovarian cancer. N Engl J Med. Supplemental Appendix. Published online December 7, 2023. doi:10.1056/NEJMoa2309169
  5. Moore K, Lorusso D, Oaknin A, et al. Integrated safety summary of single-agent mirvetuximab soravtansine in patients with folate receptor alpha (FRα)-positive recurrent ovarian cancer: phase 1 and 3 clinical trials. Poster presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; June 3–7, 2022; Chicago, IL.