Principal Investigator:
Study sponsor: Daiichi Sankyo
Location: HealthPartners Cancer Center at Regions Hospital, HealthPartners Frauenshuh Cancer Center
Phase of Study: II
Purpose of study: The purpose of the study is to determine safety and effectiveness of the study drug Partitumab Deruxtecan (also known as HER3-DXd or U3-1402). The study drug is known as an Antibody Drug Conjugate (or ADC). An antibody is a protein that is produced by the immune system to identify and get rid of foreign objects like bacteria. ADCs are composed of an antibody attached to an anticancer drug. ADCs are made to attach to tumor cells. Once attached to the cell, the ADC is taken inside the tumor cell and the anticancer drug is released inside to kill the cancer cell.
Inclusion Criteria:
– Must be at least 18 years or older.
– Must have locally advanced unresectable or metastatic disease.
– At least 1 measurable lesion per RECIST 1.1 via CT or MRI. Prostate cancer subjects with bone only lesion may be eligible.
– Able to provide pre-treatment tissue as the following: a. Tissue collected from biopsy that was performed since progressing while on, or after treatment with the most recent systemic cancer therapy prior to signing consent, OR b. patient is amenable to a pre-treatment biopsy after signing informed consent for the study. (Pretreatment tissue requirement may potentially be waived if discussed with, and approved by the medical monitor)
– ECOG of 0 – 1.
– Has adequate organ function as determined by local lab tests.
– Female patients of childbearing potential, and male patients with partners of childbearing potential must agree to use highly effective forms of birth control during the treatment period and for at least 4 months after the last dose of study drug. Additionally, female patients may not donate or retrieve ova from time of screening through at least 7 months after last dose of study drug, and male patients may not donate or freeze sperm from time of screening through 4 months after the last dose.
– Must be willing to comply with scheduled visits, drug administration plan, lab tests, and other study procedures, and must adhere to study restrictions.
Cohort specific criteria below:
– Cutaneous (acral and non-acral) melanoma:
a. Histologically or cytologically confirmed cutaneous melanoma.
b. disease progression while having received treatment with at least 1 prior line of anti-PD-1 or anti-PDL1 therapy. If patient has BRAFm melanoma, must have progressed on a BRAF/MEK inhibitor therapy as well.
– Squamous cell carcinoma of the head and neck:
c. SCC of head and neck with HPV positive or negative (as determined by local standard). Excludes primary tumor location in the nasopharynx, nasal cavity, paranasal sinuses, and unknown primary locations.
d. Disease progression after having received at least 1 and less than 3 prior lines of systemic therapy in the metastatic setting. Must have disease progression after treatment with anti-PD1/ anti-PD-L1 therapy (either as monotherapy or in combination with chemotherapy or other therapies). Must also have disease progression on PBC regimen in recurrent or metastatic setting, or in locally advanced setting with curative intent.
– Gastric or GEJ adenocarcinoma:
e. Tumor tissue confirmed as negative for HER2 expression as per ASCO-CAP guidelines. Determined prior to enrollment by local lab assessment or other accredited
f. Disease progression after treatment with at least 2 prior lines of therapy that include PBC with or without anti-PD-1 therapy.
– Ovarian carcinoma:
g. Pathologically documented high-grade serous epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
h. Documented progression at least 4 weeks after last dose of PBC and less than 6 months after last dose of PBC in the advanced / metastatic setting. Prior folate reductase alpha-targeting ADC (such as mirvetuximab soravtansine) is allowed.
– Endometrial cancer:
k. Pathologically or cytologically documented endometrial cancer, irrespective of MSI or mismatch repair status.
l. documented disease progression after at least 1 line of therapy (and maximum of 3) PBC containing systemic treatment and an anti-PD-1/ PD-L1 therapy in the advanced / metastatic setting.
– Bladder cancer:
m. Pathologically or cytologically confirmed urothelial carcinoma of the bladder, renal pelvis, ureter, or urethra. Histological variants are allowed if urothelial histology is the predominant. small cell / neuroendocrine tumors are not allowed, even if mixed histology.
n. Relapsed or progressed after treatment with at least 1 (and maximum of 3) that contains anti-PD-1/anti-PD-L1 therapy in perioperative or metastatic setting. At least 1 line of therapy must contain following treatment modalities: Chemo or enfortumab vedotin. Prior FGFR-inhibitor treatment for those who are eligible are allowed. (Required treatments can be given in combination or sequentially. Prior cisplatin-based therapy or PD-1/PD-L1 given for treatment of muscle invasive urothelial carcinoma is counted as 1 line of therapy. Same regimen administered twice in different disease settings is counted as 1 line of prior therapy)
– Esophageal Carcinoma:
o. Pathologically or cytologically documented esophageal squamous cell carcinoma.
p. must have documented disease progression after receiving 2 prior lines of therapy including previous PBC with or without anti-PD-1 therapy in advanced or metastatic setting.
– Pancreatic carcinoma:
q. Pathologically or cytologically documented unresectable or metastatic pancreatic adenocarcinoma.
r. Relapsed or disease progression after 1 prior line of systemic therapy in locally advanced / metastatic setting.
– Prostate Cancer:
s. Pathologically or cytologically documented unresectable locally advanced or metastatic CRPC.
t. Adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology.
u. Surgically or medically castrated, with testosterone levels of <50ng/dL.
v. Documented radiographic progression for patients with measurable disease after androgen deprivation.
w. Relapsed or disease progression after at least 1 of the following: abiraterone, enzalutamide, apalutamide, or darolutamide.
x. Relapsed or disease progression after receiving at least 1 cytotoxic chemotherapy that included a taxane.
*Additional criteria may apply and will be discussed with the treating physician and research team.
Exclusion Criteria:
– Has HER2-positive gastric cancer classified by ASCO-CAP guidelines prior to enrollment.
– Has Nasopharyngeal cancer.
– Has mucosal or uveal melanoma.
– Has history of ILD/pneumonitis which required corticosteroids, or has current ILD/pneumonitis.
– Has clinically significant respiratory compromise from pulmonary illnesses including but not limited to:
a. Any underlying pulmonary disorder (i.e. pulmonary emboli within 3 months prior to cycle 1 day 1, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, or pleural effusion).
b. any autoimmune or connective tissue, or inflammatory disorders (i.e. rheumatoid arthritis, Sjorgen’s syndrome, and sarcoidosis), where there is documented or suspicion of pulmonary involvement at time of screening.
c. Prior complete pneumonectomy.
-Is receiving chronic systemic corticosteroids of at least 10mg prednisone or equivalent, or any form of immunosuppressive therapy prior to cycle 1 day 1. Patients on bronchodilators, inhaled/topical steroids, or local steroid injections may be included in the study.
– Has history of, or evidence of current leptomeningeal disease.
– Has clinically significant corneal disease.
– Has evidence of clinically active spinal cord compression, or brain metastasis – defined as symptomatic or untreated, or requiring corticosteroid or anticonvulsant therapy to control symptoms. Patients with clinically inactive or treated brain mets who are asymptomatic may be included if they are neurologically stable for at least 4 weeks prior to cycle 1 day 1.
– Had inadequate washout period prior to Cycle 1 Day 1 as follows:
a. whole brain radiation within 28 days, or stereotactic radiation within 7 days.
b. cytotoxic chemo, other investigation agent, or other anticancer therapy within 14 days (or 5 half-lives, whichever is longer).
c. any ICI therapy within 21 days.
d. any mAbs other than ICIs, such as VEGF or anti-EGFR within 28 days.
e. Major surgery within 28 days.
f. Radiotherapy treatment to more than 30% of bone marrow, or wide field radiation within 28 days, or palliative radiation within 7 days.
g. Chloroquine or hydroxychloroquine within 14 days.
– Had prior treatment with anti-HER3 antibody, or ADC that contains extacecan derivative that is a topoisomerase I inhibitor.
– Has unresolved toxicities from previous anticancer therapy that has not resolved to at least grade 1 or baseline per CTCAE guidelines. (Subjects with Grade 2 toxicities that have not worsened for greater than 3 months prior to Cycle 1 Day 1 may be enrolled if toxicity is deemed manageable by the treating physician. These can include things such as: Chemo-induced neuropathy, fatigue, residual toxicities from prior immuno-oncology treatment: grade 1 or grade 2 endocrinopathies including hypo/hyperthyroidism, Type 1 diabetes, hyperglycemia, adrenal insufficiency, adrenalitis, skin hypopigmentation).
– History of other active malignancy within 3 years prior to Cycle 1 Day 1 except: adequately treated melanoma skin cancer and adequately treated thin primary melanoma <1m. Adequately treated intraepithelial carcinoma of the cervix. Any other curatively treated in situ disease. Early prostate cancer (T1-T2a, Gleason score </=6 and PSA <10ng/mL) not requiring treatment.
– Has uncontrolled or significant cardiovascular disorder prior to cycle 1 day 1.
– Has active HCV infection or uncontrolled HIV 1/2 infection. HIV infected patients must meet certain criteria to be deemed eligible.
– Has active HBV infection.
– Has evidence of severe or uncontrolled disease, psychiatric illness, social situation, geographical factors, substance abuse, or other factors that, in the treating physicians opinion would make the patient high-risk to participate in the study.
– Has known hypersensitivity to either drug substance or inactive ingredients in drug product.
– Female subject who is pregnant or breastfeeding or intends to become pregnant during the study.
– Has ongoing clinically relevant illness, medical condition, surgical history, lab finding or abnormality that, in the treating physician’s opinion, would pose risk to safety of the patient.
– Has previously received irinotecan treatment in advanced or metastatic disease setting.
*Additional criteria may apply and will be discussed with the treating physician and research team.
Study Contact:
Lisa Wahowske, RN, OCN
(651) 254-1517
Lisa.Wahowske@ParkNicollet.com
