Head and Neck Cancer Squamous Cell CarcinomaPhase 1NCT03621982
Study of ADCT-301 in Patients With Selected Advanced Solid Tumors
A Phase 1 study testing ADCT-301 and Pembrolizumab in people with Head and Neck Cancer Squamous Cell Carcinoma and Non-small Cell Lung Cancer, run by ADC Therapeutics S.A. at 9 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer Squamous Cell Carcinoma, Non-small Cell Lung Cancer, Gastric Cancer
- What is being tested?
- ADCT-301 and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 9 sitesin 3 countries
- Study dates
- 9 Nov 2018to 14 Dec 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent must be obtained prior to any procedures.
- Male or female participants 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:
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- Selected advanced solid tumors: colorectal cancer, gastric-esophageal cancer, ovarian /fallopian tube cancer, pancreatic cancer, non-small cell lung cancer, and melanoma.
- Note: For colorectal cancer, gastric-esophageal cancer, ovarian/fallopian tube cancer, pancreatic cancers mismatch repair (MMR) / microsatellite stability (MSS) / microsatellite instability (MSI) status was mandatory. If MMR/MSS/MSI status was not available at signature of the informed consent, the test should be performed before Cycle 1 Day 1 (C1D1).
- 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: Participants with advanced solid tumors and MSI-H/dMMR status, who had 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 participants with the same indication was allowed in this basket group.
- Participants who were refractory to or intolerant of existing therapy(ies) known to provide clinical benefit for their condition.
- Participants 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: Participant must have a site of disease amenable to biopsy and was willing to undergo fresh biopsy procedures (minimum 3 passes each) prior to first dose, according to the treating institution's guidelines.
- Participants 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.
- For camidanlumab tesirine in combination with pembrolizumab: Participant must either had 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 participant had received no additional anti-cancer therapy between their progression and C1D1). Participants were must 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.
- Participant with life expectancy ≥ 3 months as per Investigator assessment.
- Adequate organ function as defined by screening laboratory values within the following parameters:
- 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 were 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 participant received the last dose of camidanlumab tesirine or 4 months after last dose of pembrolizumab, whichever was the latest.
Who cannot join
- Participation in another investigational interventional study.
- Prior therapy with a CD25 (IL-2R) antibody.
- Known history of ≥Grade 3 hypersensitivity to a therapeutic antibody.
- Participants with prior solid organ or allogeneic bone marrow transplant.
- 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]) (participants with vitiligo, type 1 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).
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- 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).
- Note: An influenza test and a pathogen-directed SARS-CoV-2 test (such as polymerase chain reaction [PCR]) were mandatory and must be negative before initiating study treatment (tests to be performed 3 days or less prior to dosing on C1D1; an additional 2 days were 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 was not mandatory to be eligible but should be considered in participants with high risk for these infections; testing was mandatory if status was 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 were 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 were permissible if being tapered down). Participants 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 participants received 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 were indicated as the washout period.
- Use of any other experimental medication within 14 days prior to start of study drug (C1D1).
- Participants 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.
- 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, made the participant inappropriate for study participation or put the participant at risk.
- For participants 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.
- For participants treated with camidanlumab tesirine in combination with pembrolizumab: participants 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.
Trial locations and contacts
9 sites in 3 countries.
9 sites in 3 countries
United States5 sites
The Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Smilow Cancer Hospital Phase 1 Unit
New Haven, Connecticut, 06511
Stanford Cancer Center
Palo Alto, California, 94304
Oregon Health and Science University
Portland, Oregon, 97239
The START Center for Cancer Care
San Antonio, Texas, 78229
Belgium2 sites
Institut Jules Bordet
Anderlecht, B-1070
Universitair Ziekenhuis Gent
Ghent, 9000
United Kingdom2 sites
University College London Hospitals NHS Foundation Trust
London, England, NW1 2PG
The Christie NHS Foundation Trust
Manchester, M20 4BX
About this study
Official title: A Phase 1b, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Camidanlumab Tesirine (ADCT-301) as Monotherapy or in Combination in Patients With Selected Advanced Solid Tumors
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.
Read the detailed 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 participant was defined as the time from the date of signed written informed consent to the completion of the followup period, withdrawal of consent, loss to follow-up, or death, whichever occurs first.
The study was 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.
- Conditions
- Head and Neck Cancer Squamous Cell Carcinoma, Non-small Cell Lung Cancer, Gastric Cancer, Esophageal Cancer, Pancreas Cancer, Bladder Cancer
- Being tested
- ADCT-301, Pembrolizumab
- Keywords
- Camidanlumab tesirine
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Stomach Neoplasms, Esophageal Neoplasms, Pancreatic Neoplasms, Urinary Bladder Neoplasms, Carcinoma, Renal Cell, Melanoma, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ADCT-301Drug
Also called Camidanlumab tesirine
intravenous infusion
PembrolizumabBiological
Also called Keytruda
intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| ADCT-301 Monotherapy | Experimental | In Part 1 (dose escalation) participants received escalating doses of ADCT-301 as monotherapy.
Camidanlumab tesirine is administered as a 30-minute intravenous (IV) infusion on Day 1 of each cycle. Participants treated with camidanlumab tesirine as monotherapy, in the initial dose cohort will receive 20 μg/kg Q3W and the highest dose was 150 μg/kg Q3W. Receives: Drug: ADCT-301 |
| ADCT-301 Combination Therapy | Experimental | In Part 1 (dose escalation) participants received escalating doses of ADCT-301 in combination with pembrolizamab as combination therapy.
In Part 2 (dose expansion), participants received ADCT-301 in combination with pembrolizamab as combination therapy at the dose identified in Part 1 (dose escalation).
Participants treated with camidanlumab tesirine in combination with pembrolizumab, in the initial dose cohort received 30 μg/kg Q3W of camidanlumab tesirine.
Pembrolizumab was administered as a 30 minute IV infusion at a fixed dose of 200 mg (starting 1 hour after the end of the camidanlumab tesirine infusion). Receives: Drug: ADCT-301; Biological: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an AE that occurs or worsens in the period extending from the first dose of study drug to 30 days after the last dose of study drug in this study or start of a new anticancer therapy, whichever is earlier.
Any clinically significant changes from baseline in the safety laboratory values, vital signs, 12-lead electrocardiogram (ECG), and Eastern Cooperative Oncology Group (ECOG) performance status were reported as TEAEs.
Measured: Up to 3 years
Number of Participants Who Experienced TEAEs by Common Terminology Criteria for Adverse Events (CTCAE) Grade
AEs were graded according to CTCAE v4.0 (or more recent). For events not included in the CTCAE criteria, the severity of the AE was graded on a scale of 1 to 5, where 1 is asymptomatic or mild symptoms, 2 is moderate, 3 is severe, 4 is Life-threatening consequences and 5 is death related to an AE.
Measured: Up to 3 years
Number of Participants Who Experienced Treatment-emergent Serious Adverse Events (SAEs)
A SAE is defined as any AE that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization (hospitalization for elective procedures or for protocol compliance is not considered an SAE), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or important medical events that do not meet the preceding criteria but based on appropriate medical judgement may jeopardize the participant or may require medical or surgical intervention to prevent any of the outcomes listed above.
Measured: Up to 3 years
Number of Participants Who Experienced a SAE by CTCAE Grade
AEs were graded according to CTCAE v4.0 (or more recent). For events not included in the CTCAE criteria, the severity of the AE was graded on a scale of 1 is mild or asymptomatic, 2 is moderate, 3 is severe, 4 is Life-threatening and 5 is death related to an AE.
Measured: Up to 3 years
Number of Participants Who Experienced a Dose Interruption
Dose interruption for participants treated with ADCT-301 as monotherapy and for participants treated with ADCT-301 in combination with pembrolizumab.
Measured: Up to 3 years
Number of Participants Who Experienced a Dose Reduction
Dose reductions for participants treated with ADCT-301 as monotherapy and for participants treated with ADCT-301 in combination with pembrolizumab.
Measured: Up to 3 years
Number of Participants Who Experienced a Dose Limiting Toxicity (DLT)
For the dose-escalation of ADCT-301 as monotherapy, DLT is defined as any of the following events like hematologic DLT and non-hematologic DLT which occur during the 21 days following the first study drug administration period of Part 1, except those that are clearly due to underlying disease or extraneous causes.
For the dose-escalation of ADCT-301 in combination with pembrolizumab, a DLT is defined as any of the following events ike hematologic DLT and non-hematologic DLT which occur during the 21 days following the first study drug administration period of Part 1, except those that are clearly due to underlying disease or extraneous causes.
Measured: Day 1 to Day 21
Secondary outcomes (13)
Overall Response Rate (ORR) According to the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
The ORR was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). The overall response category was derived based on response assessment performed on or before the start of subsequent anti-cancer therapy.
Measured: Up to 3 years
Duration of Response (DOR) as Per RECIST v 1.1
DOR is defined among objective responders (CR or PR) as the time from the earliest date of first response until the first date of either disease progression (based on radiographic or clinical progression at end of treatment [EOT]/end of study [EOS]) or death due to any cause.
Measured: Up to 3 years
Progression-free Survival (PFS) as Per RECIST v 1.1
PFS defined as the time between start of treatment and the first documentation of recurrence, progression, or death for participants treated with ADCT-301 as monotherapy and for participants treated with ADCT-301 in combination with pembrolizumab.
Measured: Up to 3 years
Overall Survival (OS)
OS defined as the time between the start of treatment and death from any cause for participants treated with ADCT-301 as monotherapy and for participants treated with ADCT-301 in combination with pembrolizumab.
Measured: Up to 3 years
Time to Maximum Concentration (Tmax) of ADCT-301 in Serum Total Antibody, PBD-conjugated Antibody, and Unconjugated Warhead SG3199
The pharmacokinetic (PK) profile included determination of Tmax in serum Total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199. For participants treated with camidanlumab tesirine in combination with pembrolizumab, the collection of PK data was stopped upon consultation with the Sponsor if ADCT-301 administration is discontinued and pembrolizumab continues.
Upon consultation with the Sponsor, no further PK samples were collected, ADCT-301 was permanently discontinued and pembrolizumab continues as single agent.
Measured: Cycle 1 Day 1 (C1D1), from Pre-dose to 4 hr, 96 hr, 168 hr and 336 hr post dose; Cycle 2 Day 1 (C2D1), from Pre-dose to 4 hr, 48 hr, 96 hr, 168 hr and 336 hr post dose
Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of ADCT-301 in Serum Total Antibody, PBD-conjugated Antibody, and Unconjugated Warhead SG3199
PK profile included AUC0-last of ADCT-301 in Serum total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199. For participants treated with ADCT-301 in combination with pembrolizumab, the collection of PK data was stopped upon consultation with the Sponsor if ADCT-301 administration was discontinued and pembrolizumab continues.
Upon consultation with the Sponsor, no further PK samples were collected, ADCT-301 was permanently discontinued and pembrolizumab continues as single agent.
Measured: C1D1, from Pre-dose to 4 hr, 96 hr, 168 hr and 336 hr post dose; C2D1, from Pre-dose to 4 hr, 48 hr, 96 hr, 168 hr and 336 hr post dose
Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of ADCT-301 in Serum Total Antibody, PBD-conjugated Antibody, and Unconjugated Warhead SG3199
The PK profile included AUCinf of ADCT-301 in serum total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199. For participants treated with ADCT-301 in combination with pembrolizumab, the collection of PK data was stopped upon consultation with the Sponsor if ADCT-301 administration was discontinued and pembrolizumab continues.
Upon consultation with the Sponsor, no further PK samples were collected, ADCT-301 was permanently discontinued and pembrolizumab continues as single agent.
Measured: C1D1, from Pre-dose to 4hr, 96hr, 168 hr and 336 hr post dose; C2D1, from Pre-dose to 4 hr, 48 hr, 96 hr, 168 hr and 336 hr post dose
Area Under the Concentration-time Curve From Time Zero to the End of the Dosing Interval (AUCtau) ADCT-301 in Serum Total Antibody, PBD-conjugated Antibody, and Unconjugated Warhead SG3199
The PK profile included AUCtau ADCT-301 in serum total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199. For participants treated with ADCT-301 in combination with pembrolizumab, the collection of PK data was stopped upon consultation with the Sponsor if ADCT-301 administration was discontinued and pembrolizumab continues.
Upon consultation with the Sponsor, no further PK samples were collected, ADCT-301 was permanently discontinued and pembrolizumab continues as single agent.
Measured: C1D1, from Pre-dose to 4 hr, 96 hr, 168 hr and 336 hr post dose; C2D1, from Pre-dose to 4 hr, 48 hr, 96 hr, 168 hr and 336 hr post dose
Accumulation Index (AI) of ADCT-301 in Serum Total Antibody, PBD-conjugated Antibody and Unconjugated Warhead SG3199
The PK profile included AI of ADCT-301 in serum total antibody and PBD-conjugated antibody. For participants treated with ADCT-301 in combination with pembrolizumab, the collection of PK data was stopped upon consultation with the Sponsor if ADCT-301 administration was discontinued and pembrolizumab continues.
AI is the ratio of accumulation of a drug under steady state conditions (i.e., after repeated administration) as compared to a single dose.
Upon consultation with the Sponsor, no further PK samples were collected, ADCT-301 was permanently discontinued and pembrolizumab continues as single agent.
Measured: C2D1, from Pre-dose to 4 hr, 48 hr, 96 hr, 168 hr and 336 hr post dose
Clearance (CL) of ADCT-301 in Serum Total Antibody, PBD-conjugated Antibody and Unconjugated Warhead SG3199
The PK profile included the CL of ADCT-301 in serum total antibody and PBD-conjugated antibody. For participants treated with ADCT-301 in combination with pembrolizumab, the collection of PK data was stopped upon consultation with the Sponsor if ADCT-301 administration was discontinued and pembrolizumab continues.
Upon consultation with the Sponsor, no further PK samples were collected, ADCT-301 was permanently discontinued and pembrolizumab continues as single agent.
Measured: C1D1, from Pre-dose to 4 hr, 96 hr, 168 hr and 336 hr post dose; C2D1, from Pre-dose to 4 hr, 48 hr, 96 hr, 168 hr and 336 hr post dose
Apparent Terminal Elimination Half-life (Thalf) of ADCT-301 in Serum Total Antibody, PBD-conjugated Antibody, and Unconjugated Warhead SG3199
The PK profile included the Thalf of ADCT-301 in serum total antibody and PBD-conjugated antibody. For participants treated with ADCT-301 in combination with pembrolizumab, the collection of PK data was stopped upon consultation with the Sponsor if ADCT-301 administration was discontinued and pembrolizumab continues.
Upon consultation with the Sponsor, no further PK samples were collected, ADCT-301 was permanently discontinued and pembrolizumab continues as single agent.
Measured: C1D1, from Pre-dose to 4 hr, 96 hr, 168 hr and 336 hr post dose; C2D1, from Pre-dose to 4 hr, 48 hr, 96 hr, 168 hr and 336 hr post dose
Maximum Concentration (Cmax) of ADCT-301 in Serum Total Antibody, PBD-conjugated Antibody and Unconjugated Warhead SG3199
The PK profile included determination of Cmax in serum Total antibody, PBD-conjugated Antibody and Unconjugated Warhead SG3199. For participants treated with ADCT-301 in combination with pembrolizumab, the collection of PK data was stopped upon consultation with the Sponsor if ADCT-301 administration was discontinued and pembrolizumab continues.
Upon consultation with the Sponsor, no further PK samples were collected, ADCT-301 was permanently discontinued and pembrolizumab continues as single agent.
Measured: C1D1, from Pre-dose to 4 hr, 96 hr, 168 hr and 336 hr post dose; C2D1, from Pre-dose to 4 hr, 48 hr, 96 hr, 168 hr and 336 hr post dose
Number of Participants With Anti-drug Antibody (ADA) Response in Serum
ADA testing included number of participants with positive pre-dose ADA response, number of participants with post-dose ADA response only, and number of participants with positive ADA response at any time. Collection of ADA was stopped if ADCT-301 administration was discontinued. For participants treated with ADCT-301 in combination with pembrolizumab, unless there was a penultimate observation of positive ADA response, no other collection of ADA data was necessary if ADCT-301 administration was discontinued.
Upon consultation with the Sponsor, ADA samples were not collected anymore if ADCT-301 was permanently discontinued and pembrolizumab continues as single agent.
Measured: C1D1, from Pre-dose to 336 hr post dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2018
- Study start9 Nov 2018
- Primary completion14 Dec 2022
- Study completion14 Dec 2022
Why it stopped: Cami in combination with pembrolizumab in solid tumors showed signals of immunomodulatory activity. However, the signals were insufficiently compelling at the tested dose/schedule to justify continuation of the study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Head and Neck Cancer Squamous Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- ADC Therapeutics S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03621982
- Sponsor's protocol ID
- ADCT-301-103
- Other IDs
- 2019-003132-23, 2019
- Status last verified
- Jun 2024
- First submitted
- 28 Jun 2018
- Last updated
- 13 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Camidanlumab Tesirine (ADCT-301) as Monotherapy or in Combination in Patients With Selected Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT03621982
- Acronym / sponsor ID
- ADCT-301-103
- Conditions
- Head and Neck Cancer Squamous Cell Carcinoma, Non-small Cell Lung Cancer, Gastric Cancer, Esophageal Cancer, Pancreas Cancer, Bladder Cancer
- Keywords
- Camidanlumab tesirine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Cami in combination with pembrolizumab in solid tumors showed signals of immunomodulatory activity. However, the signals were insufficiently compelling at the tested dose/schedule to justify continuation of the study.
- Enrolment
- 78 participants (actual)
- Lead sponsor
- ADC Therapeutics S.A.Industry (pharma, biotech, devices)
- Study start
- 9 Nov 2018 (actual)
- Primary completion
- 14 Dec 2022 (actual)
- Study completion
- 14 Dec 2022 (actual)
- First posted
- 9 Aug 2018 (actual)
- Results
- Posted 13 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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 participant was defined as the time from the date of signed written informed consent to the completion of the followup period, withdrawal of consent, loss to follow-up, or death, whichever occurs first.
The study was 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ADCT-301 Monotherapy | Experimental | Drug: ADCT-301In Part 1 (dose escalation) participants received escalating doses of ADCT-301 as monotherapy. Camidanlumab tesirine is administered as a 30-minute intravenous (IV) infusion on Day 1 of each cycle. Participants treated with camidanlumab tesirine as monotherapy, in the initial dose cohort will receive 20 μg/kg Q3W and the highest dose was 150 μg/kg Q3W. |
| ADCT-301 Combination Therapy | Experimental | Drug: ADCT-301, Biological: PembrolizumabIn Part 1 (dose escalation) participants received escalating doses of ADCT-301 in combination with pembrolizamab as combination therapy. In Part 2 (dose expansion), participants received ADCT-301 in combination with pembrolizamab as combination therapy at the dose identified in Part 1 (dose escalation). Participants treated with camidanlumab tesirine in combination with pembrolizumab, in the initial dose cohort received 30 μg/kg Q3W of camidanlumab tesirine. Pembrolizumab was administered as a 30 minute IV infusion at a fixed dose of 200 mg (starting 1 hour after the end of the camidanlumab tesirine infusion). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Written informed consent must be obtained prior to any procedures.
- Male or female participants aged 18 years or older.
- Pathologic diagnosis of solid tumor malignancy that is locally advanced or metastatic at time of Screening:
- 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
- Selected advanced solid tumors: colorectal cancer, gastric-esophageal cancer, ovarian /fallopian tube cancer, pancreatic cancer, non-small cell lung cancer, and melanoma.
Key exclusion criteria (29 listed)
- Participation in another investigational interventional study.
- Prior therapy with a CD25 (IL-2R) antibody.
- Known history of ≥Grade 3 hypersensitivity to a therapeutic antibody.
- Participants with prior solid organ or allogeneic bone marrow transplant.
- 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]) (participants with vitiligo, type 1 diabetes mellitus, residual hypothyroidism, hypophysitis due to autoimmune condition only requiring hormone replacement may be enrolled).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ADCT-301Also: Camidanlumab tesirineintravenous infusion | Drug | ADCT-301 Combination Therapy, ADCT-301 Monotherapy |
| PembrolizumabAlso: Keytrudaintravenous infusion | Biological | ADCT-301 Combination Therapy |
Primary outcome
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
Time frame: Up to 3 years
An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an AE that occurs or worsens in the period extending from the first dose of study drug to 30 days after the last dose of study drug in this study or start of a new anticancer therapy, whichever is earlier. Any clinically significant changes from baseline in the safety laboratory values, vital signs, 12-lead electrocardiogram (ECG), and Eastern Cooperative Oncology Group (ECOG) performance status were reported as TEAEs.
Number of Participants Who Experienced TEAEs by Common Terminology Criteria for Adverse Events (CTCAE) Grade
Time frame: Up to 3 years
AEs were graded according to CTCAE v4.0 (or more recent). For events not included in the CTCAE criteria, the severity of the AE was graded on a scale of 1 to 5, where 1 is asymptomatic or mild symptoms, 2 is moderate, 3 is severe, 4 is Life-threatening consequences and 5 is death related to an AE.
Number of Participants Who Experienced Treatment-emergent Serious Adverse Events (SAEs)
Time frame: Up to 3 years
A SAE is defined as any AE that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization (hospitalization for elective procedures or for protocol compliance is not considered an SAE), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or important medical events that do not meet the preceding criteria but based on appropriate medical judgement may jeopardize the participant or may require medical or surgical intervention to prevent any of the outcomes listed above.
Number of Participants Who Experienced a SAE by CTCAE Grade
Time frame: Up to 3 years
AEs were graded according to CTCAE v4.0 (or more recent). For events not included in the CTCAE criteria, the severity of the AE was graded on a scale of 1 is mild or asymptomatic, 2 is moderate, 3 is severe, 4 is Life-threatening and 5 is death related to an AE.
Number of Participants Who Experienced a Dose Interruption
Time frame: Up to 3 years
Dose interruption for participants treated with ADCT-301 as monotherapy and for participants treated with ADCT-301 in combination with pembrolizumab.
Number of Participants Who Experienced a Dose Reduction
Time frame: Up to 3 years
Dose reductions for participants treated with ADCT-301 as monotherapy and for participants treated with ADCT-301 in combination with pembrolizumab.
Number of Participants Who Experienced a Dose Limiting Toxicity (DLT)
Time frame: Day 1 to Day 21
For the dose-escalation of ADCT-301 as monotherapy, DLT is defined as any of the following events like hematologic DLT and non-hematologic DLT which occur during the 21 days following the first study drug administration period of Part 1, except those that are clearly due to underlying disease or extraneous causes. For the dose-escalation of ADCT-301 in combination with pembrolizumab, a DLT is defined as any of the following events ike hematologic DLT and non-hematologic DLT which occur during the 21 days following the first study drug administration period of Part 1, except those that are clearly due to underlying disease or extraneous causes.
13 secondary outcomes
Overall Response Rate (ORR) According to the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
Time frame: Up to 3 years
Duration of Response (DOR) as Per RECIST v 1.1
Time frame: Up to 3 years
Progression-free Survival (PFS) as Per RECIST v 1.1
Time frame: Up to 3 years
Overall Survival (OS)
Time frame: Up to 3 years
Time to Maximum Concentration (Tmax) of ADCT-301 in Serum Total Antibody, PBD-conjugated Antibody, and Unconjugated Warhead SG3199
Time frame: Cycle 1 Day 1 (C1D1), from Pre-dose to 4 hr, 96 hr, 168 hr and 336 hr post dose; Cycle 2 Day 1 (C2D1), from Pre-dose to 4 hr, 48 hr, 96 hr, 168 hr and 336 hr post dose
Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of ADCT-301 in Serum Total Antibody, PBD-conjugated Antibody, and Unconjugated Warhead SG3199
Time frame: C1D1, from Pre-dose to 4 hr, 96 hr, 168 hr and 336 hr post dose; C2D1, from Pre-dose to 4 hr, 48 hr, 96 hr, 168 hr and 336 hr post dose
Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of ADCT-301 in Serum Total Antibody, PBD-conjugated Antibody, and Unconjugated Warhead SG3199
Time frame: C1D1, from Pre-dose to 4hr, 96hr, 168 hr and 336 hr post dose; C2D1, from Pre-dose to 4 hr, 48 hr, 96 hr, 168 hr and 336 hr post dose
Area Under the Concentration-time Curve From Time Zero to the End of the Dosing Interval (AUCtau) ADCT-301 in Serum Total Antibody, PBD-conjugated Antibody, and Unconjugated Warhead SG3199
Time frame: C1D1, from Pre-dose to 4 hr, 96 hr, 168 hr and 336 hr post dose; C2D1, from Pre-dose to 4 hr, 48 hr, 96 hr, 168 hr and 336 hr post dose
Accumulation Index (AI) of ADCT-301 in Serum Total Antibody, PBD-conjugated Antibody and Unconjugated Warhead SG3199
Time frame: C2D1, from Pre-dose to 4 hr, 48 hr, 96 hr, 168 hr and 336 hr post dose
Clearance (CL) of ADCT-301 in Serum Total Antibody, PBD-conjugated Antibody and Unconjugated Warhead SG3199
Time frame: C1D1, from Pre-dose to 4 hr, 96 hr, 168 hr and 336 hr post dose; C2D1, from Pre-dose to 4 hr, 48 hr, 96 hr, 168 hr and 336 hr post dose
Apparent Terminal Elimination Half-life (Thalf) of ADCT-301 in Serum Total Antibody, PBD-conjugated Antibody, and Unconjugated Warhead SG3199
Time frame: C1D1, from Pre-dose to 4 hr, 96 hr, 168 hr and 336 hr post dose; C2D1, from Pre-dose to 4 hr, 48 hr, 96 hr, 168 hr and 336 hr post dose
Maximum Concentration (Cmax) of ADCT-301 in Serum Total Antibody, PBD-conjugated Antibody and Unconjugated Warhead SG3199
Time frame: C1D1, from Pre-dose to 4 hr, 96 hr, 168 hr and 336 hr post dose; C2D1, from Pre-dose to 4 hr, 48 hr, 96 hr, 168 hr and 336 hr post dose
Number of Participants With Anti-drug Antibody (ADA) Response in Serum
Time frame: C1D1, from Pre-dose to 336 hr post dose.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
9 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ADCT-301 and Pembrolizumab in people with Head and Neck Cancer Squamous Cell Carcinoma and Non-small Cell Lung Cancer, run by ADC Therapeutics S.A. at 9 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Belgium, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) (time frame: Up to 3 years). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jun 2024.