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Posted On: 12/07/2021 2:54:26 PM
Post# of 148908
cydy presentation SABCS 2021
Publication Number: P5-17-08
A phase Ib/II study of leronlimab combined with carboplatin in patients with CCR5+ metastatic triplenegative breast cancer (mTNBC)
Massimo Cristofanilli1
, Namita Chittoria2
, Sima Ehsani3
, Hallgeir Rui4
, Milana Dolezal5
, Lisette StorkSloots6
, Femke de Snoo7
, Christopher Recknor8 and Vandana Abramson9
. 1
Robert H Lurie Comprehensive
Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL;2
Huntsman Cancer
Institute, University of Utah, Salt Lake City, UT;3
Cancer Center, University of Arizona, Tucson,
AZ;4
Medical College of Wisconsin, Milwaukee, WI;5
Alta Bates Summit Comprehensive Cancer Center,
Berkeley, CA;6
Medex15, Antwerp, Belgium7
Medex15, Amsterdam, Netherlands8
CytoDyn, Vancouver,
WA;9
Vanderbilt-Ingram Cancer Center Vanderbilt University Medical Center, Nashville, TN
M. Cristofanilli: Consulting Fees (e.g. advisory boards); Author; Novartis, Lilly, Foundation Medicine,
Menarini, Pfizer. N. Chittoria: None. S. Ehsani: None. H. Rui: None. M. Dolezal: None. L. Stork-Sloots:
Consulting Fees (e.g. advisory boards); Author; CytoDyn. F. de Snoo: Consulting Fees (e.g. advisory
boards); Author; CytoDyn. C. Recknor: Salary; Author; CytoDyn. V. Abramson: Consulting Fees (e.g.
advisory boards); Author; Eisai, Daiichi Sankyo, Abbvie. Contracted Research; Author; Genentech/Roche.
Background C-C Chemokine Ligand type-5 (CCR5) is overexpressed in >95% of TNBC and has been
correlated with disease progression. Moreover, enhancement of DNA repair signaling by CCR5 activation
may contribute to chemotherapy resistance. Therefore, blocking CCR5 may result in increased immune
response against tumor cells and synergize with chemotherapy. Leronlimab (PRO 140) is a humanized
monoclonal antibody to CCR5. Preclinical data showed leronlimab binds human CCR5, blocks CCR5-
mediated signaling, and CCL5-induced breast cancer cell invasion. The therapeutic antibody leronlimab
has been administered to over 800 healthy and HIV-1 infected individuals with good tolerance and
without obvious dose-related toxicity, making it an ideal partner for chemotherapy combinations in
TNBC.
Methods In this ongoing phase 1B/2 study, patients with CCR5+ mTNBC with ≤2 line of therapy in the
metastatic setting (no prior carboplatin) are treated with weekly subcutaneous leronlimab (3 dose
levels, 3+3 dose escalation) and a fixed dose of carboplatin AUC 5 on day 1 with a 21-day dose-limiting
toxicity (DLT) window, followed by expansion in 30 patients with CCR5+ mTNBC who are naïve to
chemotherapy in the metastatic setting or who have failed first-line combination of chemotherapy
(excluding carboplatin) and a checkpoint inhibitor in the metastatic setting. CCR5 positivity is centrally
assessed by IHC and defined as >10% CCR5 staining in primary or metastatic tumor cells and/or high
predominance of CCR5+ tumor-infiltrating leukocytes (TIL). Primary objectives are safety, tolerability,
determination of maximum tolerated dose, and determination of the recommended phase 2 dose
(RP2D).
Results Fifteen patients had archived tumor tissue assessed for CCR5 expression, with 12 being CCR5
positive (median expression 20%, range 0 - 100%, and 7 out of 12 high CCR5+ TILs) . A total of ten
patients (median age 51 years; median 2 prior therapies) have been enrolled at 3 dose levels (350, 525,
and 700 mg). In the second cohort, 1 additional patient was inadvertently enrolled. All patients
completed the DLT assessment period and no DLTs have been observed. Patients received between 3
and 27 doses of leronlimab with the number of cycles ranging from 1 to 9. Five patients remain on
treatment. The most common treatment-emergent adverse events (TEAEs) by any grade were: fatigue
(6/10), headache (4/10), constipation (3/10), and nausea (3/10). The following grade ≥3 TEAEs were
reported: neutropenia, anemia, thrombocytopenia, hyponatremia, hypertension, diarrhea and
headache. Serious Adverse Events were reported in 2 patients (grade 2 sepsis and grade 3 headache).
The following leronlimab treatment related adverse events (TRAEs) occurred (all grade 1): injection site
reaction in cohort 1, fatigue (n=2) and headache in cohort 2. Three carboplatin TRAEs ≥3 were reported
in one patient in cohort 1: thrombocytopenia, anemia and leukopenia. Two out of seven patients eligible
for response achieved a confirmed partial response, and 4 patients stable disease.
Conclusions Leronlimab, in combination with carboplatin, has been well-tolerated in all 3 dose levels
with early signs of anti-tumor activity in patients with CCR5+ mTNBC. The study is currently enrolling
patients at the RP2D dose of leronlimab 700mg in combination with carboplatin AUC 5 in the phase 2
part of the trial. Clinical trial information: NCT0383836
Publication Number: P5-17-08
A phase Ib/II study of leronlimab combined with carboplatin in patients with CCR5+ metastatic triplenegative breast cancer (mTNBC)
Massimo Cristofanilli1
, Namita Chittoria2
, Sima Ehsani3
, Hallgeir Rui4
, Milana Dolezal5
, Lisette StorkSloots6
, Femke de Snoo7
, Christopher Recknor8 and Vandana Abramson9
. 1
Robert H Lurie Comprehensive
Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL;2
Huntsman Cancer
Institute, University of Utah, Salt Lake City, UT;3
Cancer Center, University of Arizona, Tucson,
AZ;4
Medical College of Wisconsin, Milwaukee, WI;5
Alta Bates Summit Comprehensive Cancer Center,
Berkeley, CA;6
Medex15, Antwerp, Belgium7
Medex15, Amsterdam, Netherlands8
CytoDyn, Vancouver,
WA;9
Vanderbilt-Ingram Cancer Center Vanderbilt University Medical Center, Nashville, TN
M. Cristofanilli: Consulting Fees (e.g. advisory boards); Author; Novartis, Lilly, Foundation Medicine,
Menarini, Pfizer. N. Chittoria: None. S. Ehsani: None. H. Rui: None. M. Dolezal: None. L. Stork-Sloots:
Consulting Fees (e.g. advisory boards); Author; CytoDyn. F. de Snoo: Consulting Fees (e.g. advisory
boards); Author; CytoDyn. C. Recknor: Salary; Author; CytoDyn. V. Abramson: Consulting Fees (e.g.
advisory boards); Author; Eisai, Daiichi Sankyo, Abbvie. Contracted Research; Author; Genentech/Roche.
Background C-C Chemokine Ligand type-5 (CCR5) is overexpressed in >95% of TNBC and has been
correlated with disease progression. Moreover, enhancement of DNA repair signaling by CCR5 activation
may contribute to chemotherapy resistance. Therefore, blocking CCR5 may result in increased immune
response against tumor cells and synergize with chemotherapy. Leronlimab (PRO 140) is a humanized
monoclonal antibody to CCR5. Preclinical data showed leronlimab binds human CCR5, blocks CCR5-
mediated signaling, and CCL5-induced breast cancer cell invasion. The therapeutic antibody leronlimab
has been administered to over 800 healthy and HIV-1 infected individuals with good tolerance and
without obvious dose-related toxicity, making it an ideal partner for chemotherapy combinations in
TNBC.
Methods In this ongoing phase 1B/2 study, patients with CCR5+ mTNBC with ≤2 line of therapy in the
metastatic setting (no prior carboplatin) are treated with weekly subcutaneous leronlimab (3 dose
levels, 3+3 dose escalation) and a fixed dose of carboplatin AUC 5 on day 1 with a 21-day dose-limiting
toxicity (DLT) window, followed by expansion in 30 patients with CCR5+ mTNBC who are naïve to
chemotherapy in the metastatic setting or who have failed first-line combination of chemotherapy
(excluding carboplatin) and a checkpoint inhibitor in the metastatic setting. CCR5 positivity is centrally
assessed by IHC and defined as >10% CCR5 staining in primary or metastatic tumor cells and/or high
predominance of CCR5+ tumor-infiltrating leukocytes (TIL). Primary objectives are safety, tolerability,
determination of maximum tolerated dose, and determination of the recommended phase 2 dose
(RP2D).
Results Fifteen patients had archived tumor tissue assessed for CCR5 expression, with 12 being CCR5
positive (median expression 20%, range 0 - 100%, and 7 out of 12 high CCR5+ TILs) . A total of ten
patients (median age 51 years; median 2 prior therapies) have been enrolled at 3 dose levels (350, 525,
and 700 mg). In the second cohort, 1 additional patient was inadvertently enrolled. All patients
completed the DLT assessment period and no DLTs have been observed. Patients received between 3
and 27 doses of leronlimab with the number of cycles ranging from 1 to 9. Five patients remain on
treatment. The most common treatment-emergent adverse events (TEAEs) by any grade were: fatigue
(6/10), headache (4/10), constipation (3/10), and nausea (3/10). The following grade ≥3 TEAEs were
reported: neutropenia, anemia, thrombocytopenia, hyponatremia, hypertension, diarrhea and
headache. Serious Adverse Events were reported in 2 patients (grade 2 sepsis and grade 3 headache).
The following leronlimab treatment related adverse events (TRAEs) occurred (all grade 1): injection site
reaction in cohort 1, fatigue (n=2) and headache in cohort 2. Three carboplatin TRAEs ≥3 were reported
in one patient in cohort 1: thrombocytopenia, anemia and leukopenia. Two out of seven patients eligible
for response achieved a confirmed partial response, and 4 patients stable disease.
Conclusions Leronlimab, in combination with carboplatin, has been well-tolerated in all 3 dose levels
with early signs of anti-tumor activity in patients with CCR5+ mTNBC. The study is currently enrolling
patients at the RP2D dose of leronlimab 700mg in combination with carboplatin AUC 5 in the phase 2
part of the trial. Clinical trial information: NCT0383836
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