PRO1107 for Advanced Cancer

Recruiting at 5 trial locations

Overseen By Genmab Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: ProfoundBio US Co.

Must not be taking: Strong CYP3A inhibitors

Disqualifiers: Other malignancy, Active CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

280 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use a strong P450A CYP3A inhibitor within 2 weeks before joining.

What makes the drug PRO1107 unique for treating advanced cancer?

PRO1107 is an antibody-drug conjugate (ADC), which combines the targeting ability of a monoclonal antibody with the cancer-killing power of a chemotherapy drug. This design allows it to specifically target cancer cells, potentially reducing side effects compared to traditional chemotherapy. ^{1 2 3 4 5}

What is the purpose of this trial?

This is a global, open-label, multicenter Phase 1/2 study to evaluate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of GEN1107 (PRO1107) in participants with advanced solid tumors. This study consists of 2 parts, Part A: dose escalation and dose level expansion, and Part B: tumor specific expansion.

Research Team

Study Official

Principal Investigator

Genmab

Eligibility Criteria

This trial is for adults with certain advanced solid tumors, including specific types of breast, ovarian, endometrial, gastroesophageal, bladder cancer and non-small cell lung cancer. Participants must have measurable disease after prior treatments and be in good physical condition (ECOG score 0 or 1). They also need to provide a tumor sample.

Inclusion Criteria

I have been diagnosed with stomach or gastroesophageal junction cancer.

My breast cancer is triple negative.

I have been diagnosed with non-small cell lung cancer.

Exclusion Criteria

Additional protocol defined inclusion/exclusion criteria may apply

I haven't taken strong P450A CYP3A inhibitors in the last 2 weeks.

I am positive for HBV, HCV, or HIV.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Part A: Evaluation of up to 7 dose levels of PRO1107 on Day 1 of a 21-day cycle by IV infusion

21 days per cycle, multiple cycles

Dose Expansion

Part B: Initiation at a dose level based on analysis from Part A in up to 4 different cohorts

Until disease progression or other stopping criteria

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 18 months

Treatment Details

Interventions

• PRO1107

Trial Overview PRO1107 is being tested for safety and effectiveness against various advanced cancers. The study has two parts: Part A to find the right dose and expand it; Part B focuses on specific tumors. It's an open-label trial where everyone knows they're getting PRO1107.

Participant Groups

Group I: GEN1107 Experimental Treatment 1 Intervention

GEN1107 monotherapy in escalating doses in Part A and at the dose level in Part B.

Who Is Running the Clinical Trial?

ProfoundBio US Co.

Lead Sponsor

Trials

3

Recruited

750+

Genmab

Lead Sponsor

Trials

76

Recruited

15,300+

Dr. Jan van de Winkel

Genmab

Chief Executive Officer since 2010

PhD in Immunology, University of Utrecht

Dr. Judith Klimovsky

Genmab

Chief Medical Officer since 2019

MD, University of Copenhagen

Findings from Research

Antibody-drug conjugates (ADCs) combine the targeting ability of monoclonal antibodies with the cell-killing power of chemotherapy, allowing for more selective treatment of tumors, but they face challenges like low selectivity and potential premature drug release.

Recent advancements in ADC design, such as engineered antibodies that activate only in the tumor environment, aim to enhance their efficacy and safety, leading to the development of next-generation ADCs with improved therapeutic properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody-drug conjugates: Resurgent anticancer agents with multi-targeted therapeutic potential. Ceci, C., Lacal, PM., Graziani, G.[2022]

TRAIL effectively induces apoptosis in human colon tumors with minimal toxicity to normal cells, demonstrating its potential as a targeted cancer therapy.

Combining TRAIL with chemotherapy agents like 5-fluorouracil (5-FU) or CPT-11 significantly enhances antitumor effects, leading to complete tumor regression in 50% of treated mice, suggesting a promising strategy for colon cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of tumor necrosis factor-related apoptosis-inducing ligand alone and in combination with chemotherapeutic agents on patients' colon tumors grown in SCID mice. Naka, T., Sugamura, K., Hylander, BL., et al.[2018]

In a Phase 1 study involving 52 subjects with treatment-refractory metastatic castration-resistant prostate cancer, PSMA ADC was found to have an acceptable safety profile, with neutropenia and peripheral neuropathy identified as key dose-limiting toxicities.

The study demonstrated promising antitumor activity, with significant reductions in prostate-specific antigen (PSA) and circulating tumor cells (CTCs) observed at doses of 1.8 mg/kg and above, supporting further investigation of PSMA ADC as a treatment option for advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of PSMA ADC, an antibody-drug conjugate targeting prostate-specific membrane antigen, in chemotherapy-refractory prostate cancer. Petrylak, DP., Kantoff, P., Vogelzang, NJ., et al.[2021]

In a phase Ib/II trial involving 30 patients with recurrent epithelial ovarian cancer, EP0057 combined with paclitaxel showed an overall response rate of 31.6%, including one complete response, indicating potential efficacy in this difficult-to-treat population.

The treatment was well-tolerated, with no dose-limiting toxicities observed, although common side effects included decreased neutrophil count and anemia, highlighting the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase Ib/II and pharmacokinetic study of EP0057 (formerly CRLX101) in combination with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer. Duska, LR., Krasner, CN., O'Malley, DM., et al.[2021]

Recombinant TRAIL effectively induces tumor regression in mice with human colon carcinoma, showing a dose-dependent inhibition of tumor growth, especially in TRAIL-sensitive tumors.

Combining TRAIL with the chemotherapeutic agent CPT-11 significantly enhances its antitumor activity, leading to greater tumor growth inhibition and higher rates of complete tumor regression, even in initially TRAIL-resistant tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor necrosis factor-related apoptosis-inducing ligand's antitumor activity in vivo is enhanced by the chemotherapeutic agent CPT-11. Gliniak, B., Le, T.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Antibody-drug conjugates: Resurgent anticancer agents with multi-targeted therapeutic potential. [2022]

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

Effects of tumor necrosis factor-related apoptosis-inducing ligand alone and in combination with chemotherapeutic agents on patients' colon tumors grown in SCID mice. [2018]

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

Phase 1 study of PSMA ADC, an antibody-drug conjugate targeting prostate-specific membrane antigen, in chemotherapy-refractory prostate cancer. [2021]

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

A phase Ib/II and pharmacokinetic study of EP0057 (formerly CRLX101) in combination with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer. [2021]

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

Tumor necrosis factor-related apoptosis-inducing ligand's antitumor activity in vivo is enhanced by the chemotherapeutic agent CPT-11. [2018]