Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Hodgkin Disease

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Hodgkin Lymphoma

Participants received an intravenous (IV) infusion of camidanlumab tesirine (3 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 2 cycles.

Participants received an intravenous (IV) infusion of camidanlumab tesirine (5 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 4 cycles.

Participants received an intravenous (IV) infusion of camidanlumab tesirine (8 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 3 cycles.

Participants received an intravenous (IV) infusion of camidanlumab tesirine (13 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 15 cycles.

Participants received an intravenous (IV) infusion of camidanlumab tesirine (20 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 3 cycles.

Participants received an intravenous (IV) infusion of camidanlumab tesirine (30 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 10 cycles.

Participants received an intravenous (IV) infusion of camidanlumab tesirine (45 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 10 cycles.

Participants received an intravenous (IV) infusion of camidanlumab tesirine (60 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 8 cycles.

Participants received an intravenous (IV) infusion of camidanlumab tesirine (80 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 7 cycles.

Participants received an intravenous (IV) infusion of camidanlumab tesirine (100 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 5 cycles.

Participants received an intravenous (IV) infusion of camidanlumab tesirine (150 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 2 cycles.

A single participant received by error an intravenous (IV) infusion of camidanlumab tesirine (300 μg/kg) on Day 1 of Cycle 1 (planned dose was 30 μg/kg). Dosing in the subsequent cycles was 30 μg/kg (for 2 more cycles).

Camidanlumab tesirine

Jens Wuerthner, MD, PhD

This study evaluates camidanlumab tesirine in participants with relapsed/refractory Non-Hodgkin or Hodgkin lymphoma.

This is a Phase I, first in human clinical study with camidanlumab tesirine to evaluate the safety and tolerability and pharmacokinetics of camidanlumab tesirine in participants with relapsed/refractory lymphoma.

Camidanlumab tesirine is a human monoclonal antibody attached via a cleavable linker to a pyrrolobenzodiazepine (PBD) warhead which, when internalized by antigen expressing cells, covalently cross links deoxyribonucleic acid (DNA) preventing replication.

The study will be conducted in 2 parts: Part 1 (dose escalation) and Part 2 (expansion).

Study of ADCT-301 in Patients With Relapsed or Refractory Hodgkin and Non-Hodgkin Lymphoma

A Phase 1 Adaptive Dose-Escalation Study to Evaluate the Tolerability, Safety, Pharmacokinetics, and Antitumor Activity of ADCT-301 in Patients With Relapsed or Refractory Hodgkin Lymphoma and Non-Hodgkin Lymphoma

A DLT defined as any of the following, except those that are clearly due to underlying disease or extraneous causes:

A hematologic DLT is defined as (different considerations for Adult T-Cell Leukemia/Lymphoma (ATLL) participants):

* Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 febrile neutropenia or neutropenic infection
* CTCAE Grade 4 neutropenia lasting \>7 days
* CTCAE Grade 4 thrombocytopenia
* CTCAE Grade 3 thrombocytopenia with clinically significant bleeding, or Grade 3 thrombocytopenia requiring a platelet transfusion
* CTCAE Grade 4 anemia

A non-hematologic DLT is defined as:

* CTCAE Grade 4 tumor lysis syndrome
* CTCAE Grade 3 or higher AE (including nausea, vomiting, diarrhea, electrolyte imbalances lasting ≥ 48 hours despite optimal therapy; excluding all grades of alopecia)
* CTCAE Grade 3 or higher hypersensitivity reaction
* CTCAE Grade 2 or higher skin ulceration
* CTCAE Grade 2 or higher peripheral sensory or motor neuropathy

The recommended dose was established by the dose escalation steering committee and based on safety findings during Part 1 of the study.

An adverse event (AE) is defined as any untoward medical occurrence in a participant enrolled into this study regardless of its causal relationship to study drug. A TEAE is defined as any event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug.

A treatment-emergent AE (TEAE) is defined as any event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug. An SAE is defined as any event that results in death, is immediately life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.

ORR is defined as the number of participants with a best overall response of complete response (CR) or partial response (PR) at the time each participant discontinued treatment with camidanlumab tesirine.

Tumor response was assessed using the 2014 Lugano Classification.

CR is defined as achieving each of the following:

* Complete metabolic response.
* Complete radiologic response (target node regress to \<1.5 cm, no nonmeasured lesions, no organ enlargement, no new lesions and normal bone marrow morphology).

PR is defined as achieving each of the following:

* Partial metabolic response (findings indicate residual disease).
* Partial remission (\>50% decrease in target measurable nodes, regression/ absence/ no increase of nonmeasured lesions, spleen regressed by \>50% in length and no new lesions).

DoR is defined among responders (complete response \[CR\] and partial response \[PR\]) as the time from the earliest date of first response until the first date of either disease progression or death due to any cause. Tumor response was assessed using the 2014 Lugano Classification.

Disease progression is defined as progressive metabolic disease and one of the follow:

* Target node progression.
* An individual extranodal lesion must be abnormal with length \> 1.5cm and/or increase of length \> 50%.
* New or clear progression of nonmeasured lesions.
* Regrowth of previously resolved lesions or new nodes \>1.5 cm in length.
* New or recurrent bone marrow involvement.

DoR is presented overall for all participants who were classed as responders among the efficacy analysis set. Data is pooled for all lymphoma participants for DoR as specified in protocol section 8.4.

Progression-free survival (PFS) is defined among the efficacy population as the time from first dose of study drug until either disease progression or death due to any cause. Tumor response was assessed using the 2014 Lugano Classification for response.

Disease progression is defined as progressive metabolic disease and one of the following:

* Target node progression.
* An individual extranodal lesion must be abnormal with length \> 1.5cm and/or increase of length \> 50%.
* New or clear progression of nonmeasured lesions.
* Regrowth of previously resolved lesions or new nodes \> 1.5 cm in length.
* New or recurrent bone marrow involvement.

PFS is presented overall for all participants who received camidanlumab tesirine among the efficacy analysis set. Data is pooled for all lymphoma participants for PFS as specified in protocol section 8.4

Overall survival (OS) is defined as the time from the first dose of study drug treatment until the date of death due to any cause.

OS is presented overall for all participants who received camidanlumab tesirine among the efficacy analysis set. Data is pooled for all lymphoma participants for OS as specified in protocol section 8.4.

Cmax for HuMax-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC, and free warhead (SG3199).

Tmax for HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199).

AUC0-last for HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199).

AUC0-tau for HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199) for Cycle 2 only.

AUC∞ HuMax-TAC and PBD-conjugated HuMax-TAC for Cycle 1 only.

AI for HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199). AI is the ratio of area under the serum concentration-time curve (AUC) from 0 to 21 days for Cycle 2 divided by AUC from 0 to 21 days for Cycle 1 (21 day cycle length). It is the increase in drug plasma concentration after multiple dosing until a steady state is reached.

Volume of distribution for HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199).

T1/2 of HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199).

Clearance of HuMax-TAC, PBD-conjugated HuMax-TAC, and free warhead (SG3199).

An assay determines the presence of anti-ADCT-301 antibodies in human serum using a validated bridging electro chemiluminescence immunoassay (ECLIA) technique. The technique uses the drug itself to capture any anti ADCT-301 antibodies present in the serum. If anti-ADCT-301 antibodies are detected, they are confirmed to be specifically against ADCT-301 and then the level of the anti-ADCT-301 antibodies present in the serum is established using a modified version of the ECLIA technique.

ADC Therapeutics S.A.

AEs and SAEs were collected from Day 1 to 84 days after last dose (median time on treatment was 43 days \[min 1 day; max 354 days\]). All cause mortality was collected from Day 1 to End of Study (maximum of 12 months after last dose; median time on treatment was 43 days \[min 1 day; max 354 days\]).

Participants received an intravenous (IV) infusion of camidanlumab tesirine (3 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 2 cycles.

Camidanlumab tesirine: Intravenous (IV) infusion.

3 μg/kg

Participants received an intravenous (IV) infusion of camidanlumab tesirine (5 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 4 cycles.

Camidanlumab tesirine: Intravenous (IV) infusion.

5 μg/kg

Participants received an intravenous (IV) infusion of camidanlumab tesirine (8 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 3 cycles.

Camidanlumab tesirine: Intravenous (IV) infusion.

8 μg/kg

Participants received an intravenous (IV) infusion of camidanlumab tesirine (13 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 15 cycles.

Camidanlumab tesirine: Intravenous (IV) infusion.

13 μg/kg

Participants received an intravenous (IV) infusion of camidanlumab tesirine (20 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 3 cycles.

Camidanlumab tesirine: Intravenous (IV) infusion.

20 μg/kg

Participants received an intravenous (IV) infusion of camidanlumab tesirine (30 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 10 cycles.

Camidanlumab tesirine: Intravenous (IV) infusion.

30 μg/kg

Participants received an intravenous (IV) infusion of camidanlumab tesirine (45 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 10 cycles.

Camidanlumab tesirine: Intravenous (IV) infusion.

45 μg/kg

Participants received an intravenous (IV) infusion of camidanlumab tesirine (60 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 8 cycles.

Camidanlumab tesirine: Intravenous (IV) infusion.

60 μg/kg

Participants received an intravenous (IV) infusion of camidanlumab tesirine (80 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 7 cycles.

Camidanlumab tesirine: Intravenous (IV) infusion.

80 μg/kg

Participants received an intravenous (IV) infusion of camidanlumab tesirine (100 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 5 cycles.

Camidanlumab tesirine: Intravenous (IV) infusion.

100 μg/kg

Participants received an intravenous (IV) infusion of camidanlumab tesirine (150 μg/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 2 cycles.

Camidanlumab tesirine: Intravenous (IV) infusion.

150 μg/kg

A single participant received by error an intravenous (IV) infusion of camidanlumab tesirine (300 μg/kg) on Day 1 of Cycle 1 (planned dose was 30 μg/kg). Dosing in the subsequent cycles was 30 μg/kg (for 2 more cycles).

Camidanlumab tesirine: Intravenous (IV) infusion.

300 μg/kg

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

United Kingdom

Region of Enrollment

Grade 0

Grade 1

Grade 2

Grade 3

Grade 4

Grade 5

ECOG performance status was graded on a scale of 0-5, where a higher score indicated a worse outcome:

0. = fully active

1. = capable of light work of a sedentary nature
2. = capable of self-care; unable to carry out work activities
3. = capable of only limited self-care
4. = completely disabled; cannot carry out any self-care
5. = dead

Eastern Cooperative Oncology Group (ECOG) Performance Status

Weight

One participant in the 20 μg/kg group, one participant in the 30 μg/kg group and two participants in the 45 μg/kg group did not have their height measurement taken.

Height

One participant in the 20 μg/kg group, one participant in the 30 μg/kg group and two participants in the 45 μg/kg group did not have their height measurement taken, and so their Body Mass Index could not be calculated.

Body Mass Index

Clinical Trials Information

DLT Evaluable Analysis Set: The DLT-evaluable analysis set consisted of participants who completed two cycles of ADCT-301 if enrolled prior to protocol amendment 4 and participants who completed one cycle of ADCT-301 if enrolled after protocol amendment 4. The participants with completed DLT information were included even if they discontinued early before the end of cycle 2 or cycle 1 respectively.

Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

Participants with Hodgkin Lymphoma (Dose level 1: 30 µg/kg)

Participants with Hodgkin Lymphoma (Dose level 2: 45 µg/kg)

Participants with T-cell Lymphoma (80 µg/kg)

Dose-Limiting Toxicity (DLT) Evaluable Set Analysis Set

Number of participants analyzed presented in the outcome measure data are only those participants in the DLT evaluable analysis set who were dosed at the three dose levels recommended for Part 2.

Recommended Dose of Camidanlumab Tesirine for Part 2

Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE)

Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE)

Efficacy Analysis Set: The efficacy analysis set consisted of participants who received at least one dose of camidanlumab tesirine with a valid baseline and at least one valid post-baseline disease assessment or participants who had documented progression of disease or death at any time after the first dose of study.

Overall Response Rate (ORR)

Participants received an intravenous (IV) infusion of camidanlumab tesirine at any dose (doses ranging from 3 μg/kg to 300 μg/kg) on Day 1 of each 3-week treatment cycle. The maximum number of cycles received was 15.

Efficacy Analysis Set

Duration of Response (DoR)

Progression-Free Survival (PFS)

Overall Survival (OS)

Cycle 1 - HuMax-TAC

Cycle 2 - HuMax-TAC

Cycle 1 - PBD-conjugated HuMax-TAC

Cycle 2 - PBD-conjugated HuMax-TAC

Cycle 1 - Free warhead (SG3199)

Cycle 2 - Free warhead (SG3199)

Pharmacokinetic (PK) analysis set consisted of all participants who received study drug and have sufficient concentration data for PK analysis.

Maximum Observed Serum Concentration (Cmax) for Camidanlumab Tesirine

Time to Reach the Maximum Serum Concentration (Tmax) for Camidanlumab Tesirine

Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) for Camidanlumab Tesirine

Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-t) for Camidanlumab Tesirine

Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for Camidanlumab Tesirine

HuMax-TAC

PBD-conjugated HuMax-TAC

Free warhead (SG3199)

Accumulation Index (AI) for Camidanlumab Tesirine

Volume of Distribution for Camidanlumab Tesirine

Apparent Terminal Half-life (T1/2) of Camidanlumab Tesirine

Clearance of Camidanlumab Tesirine

Confirmed positive ADA pre-dose

Confirmed positive ADA post-dose only

Confirmed positive ADA at any time

Safety Analysis Set - The safety analysis set consisted of all participants who received camidanlumab tesirine.

Spots Global Cancer Trial Database for Study of ADCT-301 in Patients With Relapsed or Refractory Hodgkin and Non-Hodgkin Lymphoma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial