Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Skin and Connective Tissue Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Carcinoma, Squamous Cell

Prostatic Neoplasms

Breast Neoplasms

Triple Negative Breast Neoplasms

Melanoma

Squamous Cell Carcinoma of Head and Neck

Neoplasms by Histologic Type

Skin Diseases

Neoplasms, Glandular and Epithelial

Breast Diseases

Head and Neck Neoplasms

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Immunoglobulins

Mitoguazone

vobramitamab duocarmazine

Ashley Ward, M.D.

The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK) pharmacodynamics and preliminary antitumor activity of vobramitamab duocarmazine (MGC018) in patients with advanced solid tumors. Patients with solid tumors will be enrolled in the Dose Escalation Phase; Cohort Expansion will include metastatic castrate-resistant prostate cancer (mCRPC), non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), squamous cell carcinoma of the head and neck (SCCHN), and melanoma. Patients who do not experience unacceptable toxicity or meet criteria for permanent discontinuation may undergo additional cycles for up to two years. Patients in Cohort Expansion will be followed for survival every 3 months for 2 years following last dose.

Dose escalation will use a 3+3+3 design to identify an MAD or MTD, followed by a Cohort Expansion.

MGC018 With or Without MGA012 in Advanced Solid Tumors

A Phase 1/2, First-in-Human, Open-Label, Dose-Escalation Study of MGC018 (Anti-B7-H3 Antibody Drug Conjugate) Alone and in Combination With MGA012 (Anti-PD-1 Antibody) in Patients With Advanced Solid Tumors

Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of study drug administration through the End of Study visit.

Maximum tolerated or maximum administered dose of vobramitamab duocarmazine

The best response recorded from the start of the study treatment until the end of treatment with vobramitamab duocarmazine, taking into account any requirement for confirmation of response.

The percentage of participants who achieve a complete response (CR or partial response (PR) to treatment with vobramitamab duocarmazine

Efficacy assessed as the first dose date to the date of first documented progression using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), or death from any cause, whichever occurs first.

Efficacy assessed as the time from the date of initial objective response to the date of first documented progression RECIST v1.1, or the date of death from any cause, whichever occurs first.

Efficacy assessed as the time from the first dose date to the date of death from any cause.

Percent of prostate cancer patients with at least 50% reduction in prostate-specific antigen (PSA) with confirmation at least 3 weeks later

For prostate cancer patients, the greatest change from baseline in PSA.

Area under the plasma concentration versus time curve of vobramitamab duocarmazine

Maximum Plasma Concentration of vobramitamab duocarmazine

Time to reach maximum (peak) plasma concentration of vobramitamab duocarmazine

Trough plasma concentration of vobramitamab duocarmazine

Total body clearance of the drug from plasma of vobramitamab duocarmazine and vobramitamab duocarmazine+retifanlimab

Apparent volume of distribution at steady state of vobramitamab duocarmazine

Terminal half life of vobramitamab duocarmazine

Percent of patients with anti-drug antibodies against vobramitamab duocarmazine

MacroGenics

Niraparib

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Multiple dose levels of RP-3500 (camonsertib) for oral administration in combination with niraparib and/or Multiple dose levels of RP-3500 (camonsertib) for oral administration in combination with olaparib

Expansion cohort with RP-3500 (camonsertib) + niraparib and/or Expansion cohort RP-3500 (camonsertib) + olaparib

RP-3500 (camonsertib, ATR inhibitor) in combination with niraparib or olaparib (PARP inhibitors)

RP-3500 (camonsertib)

Gabriela Gomez, MD, MBA

Paul Basciano, MD

The primary purpose of this study is to assess the safety and tolerability of niraparib or olaparib in combination with RP-3500 (camonsertib), in patients with eligible advanced solid tumors, determine the maximum tolerated dose (MTD) of RP-3500 (camonsertib) in combination with niraparib or olaparib, examine pharmacokinetics (PK) and assess anti-tumor activity.

This is a first-in-human Phase 1b/2, multi-center, open-label, dose-escalation and expansion study to:

* Evaluate the safety profile and MTD of RP-3500 (camonsertib) when administered orally in combination with niraparib or olaparib to establish the recommended Phase 2 dose and schedule.
* Characterize the PK profile of RP-3500 (camonsertib) in combination with niraparib or olaparib
* Assess anti-tumor activity associated with RP-3500 (camonsertib) in combination with niraparib or olaparib
* Examine biomarker responses and establish a correlation with RP-3500 (camonsertib) treatment in combination with niraparib or olaparib.

After the RP2D and schedule is determined, expansion cohort(s) for RP-3500 (camonsertib) in combination with niraparib or olaparib will be enrolled to study the anti-tumor effect, and further examine the safety, PK, and pharmacodynamic (PD).

Study of RP-3500 (Camonsertib) With Niraparib or Olaparib in Advanced Solid Tumors

Phase 1b/2 Study of ATR InhibiTor RP-3500 and PARP Inhibitor Combinations in Patients With Molecularly Selected Cancers (ATTACC)

To determine the safety and tolerability of niraparib or olaparib in combination with RP-3500 (camonsertib) in patients with advanced solid tumors by assessing the grade and frequency of adverse events and serious adverse events

To define the Maximum Tolerated Dose of RP-3500-03 (camonsertib) in combination with niraparib or olaparib and determine Recommended Phase 2 Dose and preferred schedule by assessing the frequency of Dose Limiting Toxicities observed at each dose level

To preliminarily assess the antitumor activity of RP-3500 (camonsertib) with niraparib or olaparib in patients with eligible advanced solid tumors by Response evaluation criteria (RECIST 1.1 CA-125 per GCIG, and PSA per PCWG3)

To assess plasma concentrations of RP-3500 (camonsertib) and niraparib or olaparib with calculations of maximum observed plasma concentration (Cmax)

To assess plasma concentrations of RP-3500 (camonsertib) and niraparib or olaparib with calculations of time to maximum observed plasma concentration (Tmax)

To assess plasma concentrations of RP-3500 (camonsertib) and niraparib or olaparib with calculations of area under the plasma concentration-time curve 0-6 hours post dose (AUC0-6).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
MGC018 With or Without MGA012 in Advanced Solid Tumors	NCT03729596	Squamous Cell C... Triple Negative... Melanoma Advanced Solid ... Metastatic Cast... Non Small Cell ...	vobramitamab du...	18 Years -	MacroGenics
Study of RP-3500 (Camonsertib) With Niraparib or Olaparib in Advanced Solid Tumors	NCT04972110	Advanced Solid ...	RP-3500 (camons...	18 Years -	Repare Therapeutics
Study of RP-3500 (Camonsertib) With Niraparib or Olaparib in Advanced Solid Tumors	NCT04972110	Advanced Solid ...	RP-3500 (camons...	18 Years -	Repare Therapeutics
MGC018 With or Without MGA012 in Advanced Solid Tumors	NCT03729596	Squamous Cell C... Triple Negative... Melanoma Advanced Solid ... Metastatic Cast... Non Small Cell ...	vobramitamab du...	18 Years -	MacroGenics

Spots Global Cancer Trial Database for advanced solid tumor, adult