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 27 April 2022
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 Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content, Head and Neck Cancer Squamous Cell Carcinoma, Non-small Cell Lung Cancer, Gastric Cancer, Esophageal Cancer, Pancreas Cancer, Bladder Cancer, Renal Cell Carcinoma, Melanoma, Triple-negative Breast Cancer, Ovarian Cancer, Colo-rectal Cancer, Fallopian Tube Cancer
Treatment Pembrolizumab, ADCT-301
Clinical Study IdentifierNCT03621982
SponsorADC Therapeutics S.A.
Last Modified on27 April 2022

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
be performed before Cycle 1 Day 1 (C1D1)
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
Note: A maximum of 4 patients with the same indication will be allowed in this basket
group
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
C) For camidanlumab tesirine in combination with pembrolizumab: Patient must either
have a site of disease amenable to biopsy and must provide fresh tumor 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 treatment, according to the treating institution's guidelines
ECOG performance status 0-1
Patient with life expectancy ≥ 3 months as per Investigator assessment
Adequate organ function as defined by screening laboratory values within the following
Absolute neutrophil count (ANC) ≥ 1.5 × 10^3/μL (off growth factors at least 72
hours)
Platelet count ≥100 × 10^3/μL 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
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)
Blood creatinine ≤1.5 × ULN or calculated creatinine clearance ≥60 mL/min by the
Cockcroft-Gault equation
Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior
to start of study drug for women of childbearing potential (WOCBP)
Women of childbearing potential must agree to use a highly effective method of
contraception from the time of giving informed consent until at least 9.5 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 6.5 months 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
Patients with prior solid organ or allogeneic bone marrow transplant
Prior therapy with a CD25 (IL-2R) antibody
Known history of ≥Grade 3 hypersensitivity to a therapeutic antibody
History of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic
progressive sclerosis [scleroderma], systemic lupus erythematosus, Sjögren's syndrome
autoimmune vasculitis [e.g., Wegener's granulomatosis]) (patients with vitiligo, type
diabetes mellitus, residual hypothyroidism, hypophysitis due to autoimmune condition
only requiring hormone replacement may be enrolled)
History of neuropathy considered of autoimmune origin (e.g., polyradiculopathy
including Guillain-Barré syndrome and myasthenia gravis) or other central nervous
system (CNS) autoimmune disease (e.g., poliomyelitis, multiple sclerosis)
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
replacement dose steroids in the setting of adrenal insufficiency
(SARS-CoV-2)
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 dosing on C1D1; an additional
days are allowed in the event of logistical issues for receiving the results on
time)
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
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
Active bleeding diathesis or significant anticoagulation (international normalized
ratio [INR] ≥2.0)
Breastfeeding or pregnant
Significant medical comorbidities, including uncontrolled hypertension (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 myocardial infarction within 6 months prior to screening
severe uncontrolled 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
topical, inhaled, nasal, and ophthalmic steroids are allowed
Planned live vaccine within 30 days prior to the first dose of study treatment and
during study treatment
Congenital long QT syndrome, or a corrected QTcF interval of ≥ 480 ms, at screening
(unless secondary to pacemaker or bundle branch block)
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
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
For patients treated with camidanlumab tesirine in combination with pembrolizumab
patients intolerant to checkpoint-inhibitor or with a history of the following ≥ Grade
immune-related adverse events: hepatitis, renal, ocular, neurologic, cardiovascular
rheumatologic, and hematologic
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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