ADCT-601 + Gemcitabine for Cancer

Recruiting at 15 trial locations

Overseen By Contact ADC Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: ADC Therapeutics S.A.

Must not be taking: Experimental medications

Disqualifiers: Recent infection, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

128 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and assess the safety of ADCT-601 (Mipasetamab Uzoptirine), both alone and in combination with gemcitabine, for treating certain cancers. It targets cancers such as soft tissue sarcoma, pancreatic cancer, non-small-cell lung cancer (NSCLC), and others that express a specific protein called AXL. Suitable candidates for the trial include individuals with these cancers who have not responded to standard treatments and have measurable disease. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot use any other experimental medication within 14 days before starting the study drug.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Mipasetamab Uzoptirine (ADCT-601) has been tested for safety in patients with certain types of cancer, demonstrating some ability to fight cancer cells. However, limited safety information exists about its use with gemcitabine, another cancer drug.

In early studies, researchers monitored side effects while gradually increasing doses to understand how much of the drug can be given safely. As this study is in an early phase, it is still determining the safest dose levels and any possible side effects.

Gemcitabine is a well-known cancer treatment and is generally considered safe when used correctly. However, since Mipasetamab Uzoptirine is new, its full safety profile is still being developed. Participating in this clinical trial helps to learn more about the safety and effectiveness of this treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for cancers like soft tissue sarcoma, pancreatic adenocarcinoma, and non-small-cell lung cancer, which typically involve chemotherapy and radiation, Mipasetamab Uzoptirine (ADCT-601) offers a unique approach. This drug targets the AXL receptor, a protein often overexpressed in these cancers, which plays a role in tumor growth and survival. By directly targeting the AXL receptor, ADCT-601 has the potential to halt cancer progression more effectively than traditional methods. Additionally, when combined with gemcitabine, a chemotherapy agent, it could enhance the anti-cancer effects, offering a promising new option for patients with these challenging conditions. Researchers are excited about the potential of ADCT-601 to improve outcomes by specifically addressing the underlying mechanisms of these cancers.

What evidence suggests that this trial's treatments could be effective for cancer?

Research has shown that Mipasetamab Uzoptirine, also known as ADCT-601, may help treat certain cancers such as sarcoma and non-small cell lung cancer (NSCLC). Early animal studies demonstrated that it helped shrink or slow tumor growth. This treatment targets a protein called AXL, often found in large amounts in solid tumors.

In this trial, some participants will receive ADCT-601 as monotherapy, while others will receive it combined with gemcitabine, a chemotherapy drug. Gemcitabine alone has proven effective in treating cancers like pancreatic cancer, with success rates up to 54%. Together, these treatments could potentially combat several difficult-to-treat cancers. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic solid tumors, including various sarcomas and cancers like ovarian, pancreatic, bladder, cervical, and endometrial. Participants must have measurable disease and be in good physical condition (ECOG 0-1). They should not respond to standard treatments anymore. People can't join if they've had recent serious infections, chronic diarrhea conditions, symptomatic brain metastases or require frequent drainage for fluid accumulation.

Inclusion Criteria

I am fully active or can carry out light work.

My sarcoma diagnosis does not depend on AXL gene status.

I have previously been treated with a medication that includes gemcitabine.

Exclusion Criteria

I have brain metastases but have been treated and stable for over 4 weeks.

I have moderate diarrhea or a condition like IBS or IBD.

I haven't had an infection needing IV treatment in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of ADCT-601 monotherapy and in combination with gemcitabine to determine the maximum tolerated dose

8-12 weeks

Dose Expansion

Participants receive ADCT-601 monotherapy or in combination with gemcitabine to further evaluate safety and efficacy

12-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Gemcitabine
• Mipasetamab Uzoptirine (ADCT-601)

Trial Overview The study aims to find the safest dose of a new drug called Mipasetamab Uzoptirine (ADCT-601), both alone and combined with Gemcitabine chemotherapy. Researchers want to see how well patients tolerate these drugs and what effects they have on different types of solid tumors.

How Is the Trial Designed?

Group I: Part 2: Dose Expansion, ADCT-601 Monotherapy Experimental Treatment 1 Intervention

In Part 2 (dose expansion), participants with a selected indication will receive ADCT-601 monotherapy. Participants will be split into cohorts: Cohort 1: Soft tissue sarcoma (STS). Cohort 2: Pancreatic adenocarcinoma (PAAD). Cohort 3: NSCLC. Cohort 4: Solid tumors with known AXL expression.

Group II: Part 2: Dose Expansion, ADCT-601 Combination Therapy Experimental Treatment 2 Interventions

In Part 2 (dose expansion), participants with selected sarcoma indications will receive ADCT-601 in combination with gemcitabine. Participants will be split into 3 cohorts: Cohorts 5 and 6: Sarcoma indications. Cohort 7: Pancreatic cancer.

Group III: Part 1: Dose Escalation, ADCT-601 Monotherapy Experimental Treatment 1 Intervention

In Part 1 (dose escalation), participants with sarcoma indications (regardless of AXL gene amplification status), non-small-cell lung cancer (NSCLC) (regardless of AXL gene amplification status), and solid tumors with AXL gene amplification, will receive ADCT-601 monotherapy.

Group IV: Part 1: Dose Escalation, ADCT-601 Combination Therapy Experimental Treatment 2 Interventions

In Part 1 (dose escalation), participants with selected sarcoma indications will receive escalating doses of ADCT-601 in combination with gemcitabine.

Gemcitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

ADC Therapeutics S.A.

Lead Sponsor

Trials

32

Recruited

2,700+

Published Research Related to This Trial

Gemcitabine is an effective treatment for various solid tumors, including non-small-cell lung cancer and pancreatic cancer, with promising results also seen in breast and bladder cancers, based on phase II studies.

The drug has a favorable side-effect profile and may enhance the effectiveness of other DNA-damaging agents, suggesting its potential for use in combination therapies and different treatment schedules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of gemcitabine in the treatment of other tumours. Carmichael, J.[2022]

Gemcitabine, a nucleoside analog, inhibits DNA synthesis and shows potential synergy with other antimetabolites like 5-fluorouracil, making it a promising treatment for solid tumors.

In a phase I study involving eight patients, the main side effect observed was myelosuppression, and the study aims to establish the maximum tolerated doses of gemcitabine when combined with UFT and oral calcium folinate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and UFT plus oral calcium folinate: phase I study. Philip, PA., Ibrahim, D., Zalupski, M., et al.[2022]

Gemcitabine (GEMZAR) has shown to be an effective treatment for non-small-cell lung cancer (NSCLC) with a response rate of about 21% as a single agent, and it has a mild toxicity profile, making it suitable for combination therapies.

When combined with cisplatin, gemcitabine achieved higher response rates ranging from 38% to 54% and median survival times of 8.4 to 14.3 months, with manageable side effects, indicating its potential as a preferred treatment option in NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination studies with gemcitabine in the treatment of non-small-cell lung cancer. Steward, WP.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05389462

NCT05389462 | A Study of Mipasetamab Uzoptirine (ADCT ... A Phase 1b, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of ...

2. adctmedical.com adctmedical.com/wp-content/uploads/2024/04/AACR-2024_Van-Tine_ADCT-601-102-dose-esc-STS_poster_FINAL_crtd-1.pdf

Phase 1b Trial Mipasetamab Uzoptirine (ADCT-601-102) ... AXL is a cell surface receptor tyrosine kinase widely expressed in solid tumors, including sarcomas1. ○ AXL overexpression is linked to ...

3. aacrjournals.org aacrjournals.org/cancerres/article/84/7_Supplement/CT059/742424/Abstract-CT059-Phase-1b-trial-Mipasetamab

Phase 1b trial Mipasetamab Uzoptirine (ADCT-601-102) dose ... Mipa demonstrated antitumor activity in pre-clinical mice models of sarcoma, adrenocortical carcinoma and pancreatic cancer, and clinical ...

4. withpower.com withpower.com/trial/phase-1-neoplasms-5-2022-48df3

ADCT-601 + Gemcitabine for Cancer · Info for Participants Gemcitabine has shown effectiveness in treating various cancers, including non-small-cell lung cancer and pancreatic cancer, with response rates of up to 54% ...

5. trialx.com trialx.com/clinical-trials/listings/227894/a-study-of-mipasetamab-uzoptirine-adct-601-in-participants-with-solid-tumors/

A Study of Mipasetamab Uzoptirine (ADCT-601) in ... Overview. The primary objective of this study is to identify the recommended phase 2 dose (RP2D) and/or the maximum tolerated dose (MTD), and characterize ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9377743/

Preclinical Development of ADCT-601, a Novel ... Safety and tolerability. Safety and tolerability of ADCT-601 in non–tumor-bearing male Sprague-Dawley rats were determined following single-dose ...