Study of ADCT-301 in Patients With Selected Advanced Solid Tumors

  • STATUS
    Recruiting
  • End date
    Nov 15, 2023
  • participants needed
    95
  • sponsor
    ADC Therapeutics S.A.
Updated on 3 December 2021
platelet count
gonadotropin
cancer
beta-human chorionic gonadotropin
measurable disease
carcinoma
direct bilirubin
growth factor
lung cancer
gilbert's syndrome
human chorionic gonadotropin
metastasis
neutrophil count
total abstinence
esophageal cancer
pembrolizumab
blood transfusion
programmed cell death 1 ligand 1
conjugated bilirubin
solid tumour
solid tumor
beta human chorionic gonadotropin
fallopian tube
esophagus cancer
pancreatic cancers
cancer of the ovary
lung carcinoma

Summary

This study evaluates ADCT-301 in patients with Selected Advanced Solid Tumors. Patients will participate in a Treatment Period with 3-week cycles and a Follow-up Period every 12 weeks for up to 1 year after treatment discontinuation.

Description

This is a Phase 1b, multi-center, open-label study with a dose-escalation part and a dose expansion part.

The duration of the study participation for each patient is defined as the time from the date of signed written informed consent to the completion of the follow-up period, withdrawal of consent, loss to follow-up, or death, whichever occurs first.

The study will include a Screening Period (of up to 21 days), a Treatment Period (with cycles of 3 weeks for a Q3W dosing regimen), and a Follow-up Period (approximately every 12 week visits) for up to 1 year after treatment discontinuation

Details
Condition Malignant neoplasm of prostate, Pancreatic Cancer, Non-Small Cell Lung Cancer, Adenocarcinoma, urinary tract neoplasm, Ovarian disorder, Colorectal Cancer, Malignant neoplasm of kidney, Prostatic disorder, bladder cancer, bladder disorder, Breast Cancer, Fallopian Tube Cancer, Ovarian Cancer, Esophageal Diseases, Esophageal Cancer, melanoma, Renal Cell Carcinoma, skin cancer, Gastropathy, Gastric Cancer, head and neck cancer, Diet and Nutrition, Chronic Diarrhea, Stomach Discomfort, Skin Wounds, Metastatic Melanoma, Chronic Shoulder Pain, Prostate Disorders, Vaginal Atrophy, Adverse Effects, Drugs, Injection Port, Breast Cancer - HER2 Positive, Anal Dysplasia, Primary Immunodeficiency, Pediatric Health, Near-Sighted Corrective Surgery, Colon Cancer Screening, Prostate Cancer, Early, Recurrent, Colon cancer; rectal cancer, Ovarian Function, Esophageal Carcinoma, Peripheral Arterial Occlusive Disease, Triple Negative Breast Cancer, Brain Function, Urothelial Cancer, Gastric Carcinoma, Recurrent Respiratory Papillomatosis, Recurrent Ovarian Cancer, Razor Bumps (Pseudofolliculitis Barbae), Islet Ce417ll Cancer, Metastatic Triple-Negative Breast Cancer, Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content, Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content, Kidney Cancer, Prostate Cancer, Esophageal Disorders, Malignant Melanoma, Malignant Adenoma, Stomach Cancer, Bladder Disorders, Renal Cell Cancer, Renal Cancer, Bladder Carcinoma, Urologic Cancer, Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content, Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content, Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content, Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content, Head and Neck Cancer Squamous Cell Carcinoma, Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content, Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content, Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content, Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content, Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content, clear cell renal cell carcinoma, ovarian carcinomas, cancer, ovarian, cancer ovarian, cancer of the ovary, gastric cancers, carcinoma of the bladder, esophagus cancer, oesophageal cancer, nsclc, fallopian tube cancers, cancer of the pancreas, ovarian tumors, pancreatic cancers, cancer, pancreatic, cancer of the esophagus, oesophageal carcinoma, bladder tumor, Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content, Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content, Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content, Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content, Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content, Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content, Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content, Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content, Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content, Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content, Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content, Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content, Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content
Treatment Pembrolizumab, ADCT-301
Clinical Study IdentifierNCT03621982
SponsorADC Therapeutics S.A.
Last Modified on3 December 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Written informed consent must be obtained prior to any procedures
Male or female patient aged 18 years or older
Pathologic diagnosis of solid tumor malignancy that is locally advanced or metastatic at time of Screening
Part 1 Dose escalation camidanlumab tesirine as monotherapy
Selected advanced solid tumors: colorectal, head and neck, NSCLC, gastric and
esophageal cancers, pancreas, bladder, renal cell carcinoma, melanoma, TNBC
and ovarian/fallopian tube cancers
Part 1 Dose-escalation camidanlumab tesirine in combination with
pembrolizumab
Selected advanced solid tumors: colorectal cancer, gastric-esophageal cancer
ovarian /fallopian tube cancer, pancreatic cancer, non-small cell lung cancer
and melanoma
Part 2 Dose expansion camidanlumab tesirine in combination with pembrolizumab
Note: For colorectal cancer, gastric-esophageal cancer, ovarian/fallopian tube
Group 1: One of the indications identified in Part 1, for which at least 1 response (PR or CR) was seen
cancer, pancreatic cancers mismatch repair (MMR) / microsatellite stability
(MSS) / microsatellite instability (MSI) status is mandatory. If MMR/MSS/MSI
parameters
status is not available at signature of the informed consent, the test should
Absolute neutrophil count (ANC) 1.5 10^3/L (off growth factors at least 72 hours)
be performed before Cycle 1 Day 1 (C1D1)
Platelet count 100 10^3/L without transfusion in the past 10 days
Hemoglobin 9 g/dL (5.6 mmol/L) (prior transfusion allowed)
Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or gamma glutamyl transferase (GGT) 2.5 the upper limit of normal (ULN) if there is no liver involvement; ALT or AST 5 ULN if there is liver involvement
Group 2: Patients with advanced solid tumors and MSI-H/dMMR status, who have received a prior regimen containing PD-1/PD-L1 inhibitors, for which the best response was CR, PR, or SD 4 months, and then progressed while under treatment with the PD-1/PD-L1 inhibitor-based regimen
Total bilirubin 1.5 ULN (patients with known Gilbert's syndrome may have a total bilirubin up to 3 ULN with direct bilirubin 1.5 ULN)
Note: A maximum of 4 patients with the same indication will be allowed in this
Blood creatinine 1.5 ULN or calculated creatinine clearance 60 mL/min by the Cockcroft-Gault equation
basket group
Negative beta-human chorionic gonadotropin (-HCG) pregnancy test within 7 days prior to start of study drug for women of childbearing potential (WOCBP)
\. Patients who are refractory to or intolerant of existing therapy(ies)
known to provide clinical benefit for their condition
\. Patients with advanced/metastatic cancer, with measurable disease as
determined by RECIST v1.1 or immune-related Response Criteria (irRC)/ immune-
related Response Evaluation Criteria In Solid Tumors (irRECIST)/ immune-
related Response Evaluation Criteria In Solid Tumors (iRECIST)/ immune-
modified Response Evaluation Criteria in Solid Tumors (imRECIST) as per
Investigator discretion
\. A) For camidanlumab tesirine as monotherapy: Patient must have a site of
disease amenable to biopsy and be willing to undergo fresh biopsy procedures
(minimum 3 passes each) prior to first dose, according to the treating
institution's guidelines
B) Patients included in the paired-biopsy cohort must in addition be willing
to undergo fresh biopsy procedures (minimum 3 passes each) after receiving at
least 1 dose of study drug
either have a site of disease amenable to biopsy and must provide fresh tumor
C) For camidanlumab tesirine in combination with pembrolizumab: Patient must
biopsy prior to C1D1, or have sufficient available archival tumor tissue
(biopsied after their last disease progression, and in the situation where the
patient has received no additional anti-cancer therapy between their
progression and C1D1). Patients must also be willing to undergo fresh biopsy
procedures (minimum 3 passes each) after receiving at least 1 dose of study
\. ECOG performance status 0-1
treatment, according to the treating institution's guidelines
\. Patient with life expectancy 3 months as per Investigator assessment
\. Adequate organ function as defined by screening laboratory values within
the following
Women of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 6.5 months after the last dose of camidanlumab tesirine or 4 months after last dose of pembrolizumab, whichever is the latest. Men with female partners who are of childbearing potential must agree to use a condom when sexually active or practice total abstinence from the time of giving informed consent until at least 16 weeks after the patient receives his last dose of camidanlumab tesirine or 4 months after last dose of pembrolizumab, whichever is the latest

Exclusion Criteria

Participation in another investigational interventional study
Known history of Grade 3 hypersensitivity to a therapeutic antibody
Patients with prior solid organ or allogeneic bone marrow transplant
History of neuropathy considered of autoimmune origin (e.g., polyradiculopathy including Guillain-Barr syndrome and myasthenia gravis) or other central nervous system (CNS) autoimmune disease (e.g., poliomyelitis, multiple sclerosis)
Note: An influenza test and a pathogen-directed SARS-CoV-2 test (such as
polymerase chain reaction [PCR]) are mandatory and must be negative before
initiating study treatment (tests to be performed 3 days or less prior to
\. Known seropositive and requiring anti-viral therapy for human
immunodeficiency (HIV) virus, hepatitis B virus (HBV), or hepatitis C virus
(HCV). Note: Testing is not mandatory to be eligible but should be considered
in patients with high risk for these infections; testing is mandatory if
status is unknown
\. History of Stevens-Johnson syndrome or toxic epidermal necrolysis
\. Failure to recover to Grade 1 (Common Terminology Criteria for Adverse
Events version 4.0 [CTCAE version 4.0]) from acute nonhematologic toxicity (to
Grade 2 for neuropathy or alopecia), due to previous therapy, prior to
screening
\. Symptomatic CNS metastases or evidence of leptomeningeal disease (brain
MRI or previously documented cerebrospinal fluid [CSF] cytology). Previously
treated asymptomatic CNS metastases are permitted provided that the last
treatment (systemic anticancer therapy and/or local radiotherapy) was
completed 4 weeks prior to Day 1 except usage of low dose of steroids on a
taper (i.e., up to 10 mg prednisone or equivalent on Day 1 and consecutive
days is permissible if being tapered down). Patients with discrete dural
metastases are eligible
\. Clinically significant third space fluid accumulation (i.e., ascites
requiring drainage or pleural effusion that is either requiring drainage or
associated with shortness of breath)
\. Active diarrhea CTCAE Grade 2 or a medical condition associated with
chronic diarrhea (such as irritable bowel syndrome, inflammatory bowel
disease)
\. Active infection requiring systemic antibiotic therapy
Prior therapy with a CD25 (IL-2R) antibody
\. Active bleeding diathesis or significant anticoagulation (international
normalized ratio [INR] 2.0)
History of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, Sjgren's syndrome, autoimmune vasculitis [e.g., Wegener's granulomatosis]) (patients with vitiligo, type 1 diabetes mellitus, residual hypothyroidism, hypophysitis due to autoimmune condition only requiring hormone replacement may be enrolled)
\. Breastfeeding or pregnant
\. Significant medical comorbidities, including uncontrolled hypertension
History of recent infection (within 4 weeks of C1D1) caused by a pathogen known to be associated with GBS, for example: herpes simplex virus 1/2 (HSV1, HSV2), varicella zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), measles, Influenza A, Zika virus, Chikungunya virus, mycoplasma pneumonia, Campylobacter jejuni, enterovirus D68, or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
(blood pressure [BP] 160 mmHg systolic and/or 110 mmHg diastolic repeatedly
with or without anti hypertensive medication), unstable angina, congestive
heart failure (greater than New York Heart Association class II)
electrocardiographic evidence of acute ischemia, coronary angioplasty or
dosing on C1D1; an additional 2 days are allowed in the event of logistical
myocardial infarction within 6 months prior to screening, severe uncontrolled
issues for receiving the results on time)
atrial or ventricular cardiac arrhythmia, poorly controlled diabetes, active
ulceration of the upper gastrointestinal (GI) tract or GI bleeding, or severe
chronic pulmonary disease
\. Major surgery, radiotherapy, chemotherapy or other anti-neoplastic
therapy within 14 days prior to start of study drug (C1D1), except shorter if
approved by the Sponsor. For cytotoxic agents that have major delayed
toxicity, e.g., mitomycin C and nitrosoureas, 4 weeks is indicated as washout
period. For patients receiving systemic anticancer immunotherapies (as opposed
to intralesional) that lead to activation of Teffs and/or increase the
Teff/Treg ratio, such as anti-PD-1 antibodies, 4 weeks are indicated as the
washout period
\. Use of any other experimental medication within 14 days prior to start of
study drug (C1D1)
\. Patients requiring concomitant immunosuppressive agents or chronic
treatment with corticosteroids except
replacement dose steroids in the setting of adrenal insufficiency
topical, inhaled, nasal, and ophthalmic steroids are allowed. 21. Planned live vaccine within 30 days prior to the first dose of study treatment and during study treatment. 22. Congenital long QT syndrome, or a corrected QTcF interval of 480 ms, at screening (unless secondary to pacemaker or bundle branch block). 23. Active second primary malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that the Sponsor's medical monitor and Investigator agree and document should not be exclusionary. 24. Any other significant medical illness, abnormality, or condition that would, in the Investigator's judgment, make the patient inappropriate for study participation or put the patient at risk. 25. For patients treated with camidanlumab tesirine in combination with pembrolizumab: patients intolerant to checkpoint-inhibitor or with a history of the following Grade 3 immune-related adverse events: hepatitis, renal, ocular, neurologic, cardiovascular, rheumatologic, and hematologic. 26. For patient treated with camidanlumab tesirine in combination with pembrolizumab: patients with a history of non-infectious pneumonitis related to prior systemic treatment and that require treatment with steroids within the last 6 months prior to enrollment
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