ADCT-601 + Gemcitabine for Cancer

Recruiting at 13 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

260 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective of this study is to identify the recommended phase 2 dose (RP2D) and/or the maximum tolerated dose (MTD), and characterize the safety and tolerability of ADCT-601 monotherapy and in combination with gemcitabine.

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.

What data supports the effectiveness of the drug Gemcitabine (Gemzar) in cancer treatment?

Gemcitabine has shown effectiveness in treating various cancers, including non-small-cell lung cancer and pancreatic cancer, with response rates of up to 54% when combined with other drugs like cisplatin. It has also been effective in breast, bladder, ovarian, and head and neck cancers, often with mild side effects. ^{1 2 3 4 5}

Is the combination of ADCT-601 and Gemcitabine safe for humans?

Gemcitabine, also known as Gemzar, has been studied in many clinical trials and is generally well tolerated with mild side effects like temporary low blood cell counts, mild nausea, and flu-like symptoms. Serious side effects are rare, but some patients have experienced temporary kidney issues and mild swelling. There is no specific safety data available for ADCT-601 (Mipasetamab Uzoptirine) in combination with Gemcitabine. ^{1 2 6 7 8}

What makes the drug ADCT-601 + Gemcitabine unique for cancer treatment?

The combination of ADCT-601 (Mipasetamab Uzoptirine) with Gemcitabine is unique because it pairs a novel antibody-drug conjugate with a well-established chemotherapy agent, potentially enhancing the effectiveness against solid tumors by targeting cancer cells more precisely while utilizing Gemcitabine's ability to inhibit DNA synthesis. ^{1 3 9 10 11}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Gemcitabine and UFT plus oral calcium folinate: phase I study. [2022]

2. England pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

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

4. United States pubmed.ncbi.nlm.nih.gov

Gemcitabine and paclitaxel in metastatic breast cancer: a review. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Gemcitabine and platinum-based chemotherapy in metastatic breast cancer. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Gemcitabine--a safety review. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of gemcitabine-fluorouracil combination therapy in the management of advanced pancreatic cancer: a meta-analysis of randomized controlled trials. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Antitumour activity of sunitinib in combination with gemcitabine in experimental pancreatic cancer. [2022]

9. France pubmed.ncbi.nlm.nih.gov

[Gemcitabine: from preclinic to clinic passing by pharmacokinetics]. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Cross-resistance in the 2',2'-difluorodeoxycytidine (gemcitabine)-resistant human ovarian cancer cell line AG6000 to standard and investigational drugs. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Increased sensitivity to gemcitabine of P-glycoprotein and multidrug resistance-associated protein-overexpressing human cancer cell lines. [2022]