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

NCT03621982 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: ADCT-301-1032019-003132-23
• Study Type: interventional
• Target: 78
• Locations: 3 countries
• Sites: 9

Brief 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.

Conditions

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

Keywords

Camidanlumab tesirine

Outcome Measures

Primary Outcomes (7)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  Day 1 to Day 21

Secondary Outcomes (13)

• Overall Response Rate (ORR) According to the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.

  Up to 3 years

• Duration of Response (DOR) as Per RECIST v 1.1

  Up to 3 years

• Progression-free Survival (PFS) as Per RECIST v 1.1

  Up to 3 years

• Overall Survival (OS)

  Up to 3 years

• Time to Maximum Concentration (Tmax) of ADCT-301 in Serum Total Antibody, PBD-conjugated Antibody, and Unconjugated Warhead SG3199

  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

Study Arms (2)

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.

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).

Drug: ADCT-301; Biological: Pembrolizumab

Interventions

ADCT-301 DRUG

intravenous infusion

Also known as: Camidanlumab tesirine

ADCT-301 Combination Therapy; ADCT-301 Monotherapy

Pembrolizumab BIOLOGICAL

intravenous infusion

Also known as: Keytruda

ADCT-301 Combination Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• ADC Therapeutics S.A.: lead

Study Sites (9)

Stanford Cancer Center

Palo Alto, California, 94304, United States

Location

Smilow Cancer Hospital Phase 1 Unit

New Haven, Connecticut, 06511, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

The Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

The START Center for Cancer Care

San Antonio, Texas, 78229, United States

Location

Institut Jules Bordet

Anderlecht, B-1070, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

University College London Hospitals NHS Foundation Trust

London, England, NW1 2PG, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Stomach Neoplasms; Esophageal Neoplasms; Pancreatic Neoplasms; Urinary Bladder Neoplasms; Carcinoma, Renal Cell; Melanoma; Triple Negative Breast Neoplasms; Ovarian Neoplasms; Colonic Neoplasms; Fallopian Tube Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Kidney Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Breast Diseases; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Genital Diseases; Gonadal Disorders; Colorectal Neoplasms; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Fallopian Tube Diseases

Results Point of Contact

• Title: Yvan LeBruchec
• Organization: ADC Therapeutics

Yvan.LeBruchec@adctherapeutics.com

+41799110551

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2018
• First Posted: August 9, 2018
• Study Start: November 9, 2018
• Primary Completion: December 14, 2022
• Study Completion: December 14, 2022
• Last Updated: June 13, 2024
• Results First Posted: June 13, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2); US (5); BE (2)