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.
This is a Phase 1b, multi-center, open-label study with a dose-escalation part and a dose
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
|Overal Status||Start Date||Phase||Study Type|
|Recruiting||November 9, 2018||Phase 1||Interventional|
Primary Outcome 1 - Measure: Assessment of Dose Limiting Toxicities in Determination of the Maximum Tolerated Dose Limiting toxicities as defined per protocol, as related to ADCT-301
Primary Outcome 1 - Time Frame: Up to 3 years
Primary Outcome 2 - Measure: Number of Adverse Events of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or Above
Primary Outcome 2 - Time Frame: Up to 3 years
Primary Outcome 3 - Measure: Number of Serious Adverse Events (SAE)
Primary Outcome 3 - Time Frame: Up to 3 years
Primary Outcome 4 - Measure: Number of SAEs of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or Above
Primary Outcome 4 - Time Frame: Up to 3 years
Primary Outcome 5 - Measure: Number of Dose Interruptions and/or Dose Reductions
Primary Outcome 5 - Time Frame: Up to 3 years
Primary Outcome 6 - Measure: Number of Dose Limiting Toxicities
Primary Outcome 6 - Time Frame: Up to 3 years
Primary Outcome 7 - Measure: Number of Participants who Experience a Clinically Significant Change in Baseline in Laboratory Values
Primary Outcome 7 - Time Frame: Up to 3 years
Primary Outcome 8 - Measure: Number of Participants who Experience a Clinically Significant Change in Baseline in Vital Signs
Primary Outcome 8 - Time Frame: Up to 3 years
Primary Outcome 9 - Measure: Number of Participants who Experience a Clinically Significant Change in Baseline in Electrocardiogram (ECG) Results
Primary Outcome 9 - Time Frame: Up to 3 years
Primary Outcome 10 - Measure: Number of Particpants who Experience a Clinically Significant Change in Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status
Primary Outcome 10 - Time Frame: Up to 3 years
1. Written informed consent must be obtained prior to any procedures.
2. Male or female patient aged 18 years or older.
3. Pathologic diagnosis of solid tumor malignancy that is locally advanced or metastaticr/> 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:
- Group 1: One of the indications identified in Part 1, for which at least 1
response (PR or CR) was seen.
- Group 2: Selected advanced solid tumors: colorectal cancer, gastric-esophageal
cancer, ovarian/fallopian tube cancer, pancreatic cancer, non-small cell lung
cancer, melanoma, with the exception for the one selected for Group 1.
4. Patients who are refractory to or intolerant of existing therapy(ies) known to provide
clinical benefit for their condition.
5. 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.
6. 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 have a
site of disease amenable to biopsy and must provide fresh tumor biopsy prior to C1D1,
and 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
7. ECOG performance status 0-1.
8. Adequate organ function as defined by screening laboratory values within the following
1. Absolute neutrophil count (ANC) ≥ 1.5 × 10^3/μL (off growth factors at least 72
2. Platelet count ≥100 × 10^3/μL without transfusion in the past 10 days.
3. Hemoglobin ≥9 g/dL (5.6 mmol/L) (prior transfusion allowed).
4. 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.
5. 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).
6. Blood creatinine ≤1.5 × ULN or calculated creatinine clearance ≥60 mL/min by the
9. Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior
to start of study drug for women of childbearing potential (WOCBP).
10. Women of childbearing potential* must agree to use a highly effective** method of
contraception from the time of giving informed consent until at least 16 weeks 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.
1. Participation in another investigational interventional study.
2. Prior therapy with a CD25 (IL-2R) antibody within the last 4 months.
3. Known history of ≥Grade 3 hypersensitivity to a therapeutic antibody.
4. Patients with prior solid organ or allogeneic bone marrow transplant.
5. 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
I diabetes mellitus, residual hypothyroidism, hypophysitis due to autoimmune condition
only requiring hormone replacement may be enrolled).
6. 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).
7. 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 (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).
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).
8. 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.
9. History of Stevens-Johnson syndrome or toxic epidermal necrolysis.
10. 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.
11. 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.
12. 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).
13. Active diarrhea CTCAE Grade 2 or a medical condition associated with chronic diarrhea
(such as irritable bowel syndrome, inflammatory bowel disease).
14. Active infection requiring systemic antibiotic therapy.
15. Active bleeding diathesis or significant anticoagulation (international normalized
ratio [INR] ≥2.0).
16. Breastfeeding or pregnant.
17. 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.
18. 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.
19. Use of any other experimental medication within 14 days prior to start of study drug
20. Patients requiring concomitant immunosuppressive agents or chronic treatment with
- 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
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No
Name: ADC Therapeutics
|Stanford Cancer Center
Palo Alto, California 94304
Sukhmani K Padda, MD
|Smilow Cancer Hospital Phase 1 Unit
New Haven, Connecticut 06511
Patricia LoRusso, DO
|Roswell Park Cancer Institute
Buffalo, New York 14263
Igor Puzanov, MD
|The Sarah Cannon Research Institute
Nashville, Tennessee 37203
Johanna C Bendell, MD
|South Texas Accelerated Research Therapeutics, LLC
San Antonio, Texas 78229
Kyriakos P Papadopoulos, MD