Study of RP-3500, Camonsertib, in Advanced Solid Tumors

Conditions

Advanced Solid Tumor

Keywords

Adult

Brief summary

The primary purpose of this study is to define the maximum tolerated dose (MTD) and determine a recommended Phase 2 dose (RP2D) and schedule of orally-administered RP-3500 (camonsertib) alone or in combination with talazoparib, a PARP inhibitor, or Gemcitabine in patients with advanced solid tumors with ATR inhibitor-sensitizing mutations. This study will also evaluate the safety and tolerability of RP-3500 (camonsertib) alone or in combination with talazoparib or gemcitabine, examine both the pharmacokinetics (PK)and pharmacodynamics (PD)and investigate its anti-tumor activity in solid tumors.

Detailed description

This is a first-in-human, Phase 1/2a, multi-center, open-label, dose-escalation and expansion study to: * Evaluate the safety profile and MTD of RP-3500 (camonsertib) when administered orally, alone and in combination with talazoparib or gemcitabine, to establish the dose and schedule recommended for the Phase 2 * Characterize the PK profile of RP-3500 (camonsertib) alone or in combination with talazoparib or gemcitabine * Identify anti-tumor activity associated with RP-3500 (camonsertib) given alone or in combination with talazoparib or gemcitabine The initial cohorts will test RP-3500 (camonsertib) as monotherapy. Additional cohorts will enroll with RP-3500 (camonsertib) in combination with talazoparib or gemcitabine. After the RP2D and schedule is determined, expansion cohort(s) for RP-3500 (camonsertib) will be enrolled to study the anti-tumor effect, and further examine the safety and PK of RP-3500 (camonsertib) at the RP2D

Rosen EY, Yap TA, Fontana E, Lee EK, Mahalingam D, Højgaard M, Mettu NB, Cote GM, Plummer R, Koehler M, Ulanet D, Fei K, Silverman IM, Schonhoft JD, Rimkunas V, Bacque ES, Gomez G, Fretland AJ, Roulston A, Li L, Baruah P, Zimmermann M, Yang J, Carneiro BA, Lheureux S.

2026-01-21

10.1158/1078-0432.ccr-25-2240

Genomic and Epigenomic ctDNA Profiling in Liquid Biopsies from Heavily Pretreated Patients with DNA Damage Response-Deficient Tumors.

Silverman IM, Schonhoft JD, Herzberg B, Yablonovitch A, Lagow E, Fiaux PC, Safabakhsh P, Sethuraman S, Ulanet D, Yang J, Kim I, Basciano P, Cecchini M, Lee E, Lheureux S, Fontana E, Carneiro BA, Reis-Filho JS, Yap TA, Zinda M, Rosen EY, Rimkunas V.

2025-10-01

10.1158/1078-0432.ccr-25-1248

Data from Genomic and Epigenomic ctDNA Profiling in Liquid Biopsies from Heavily Pretreated Patients with DNA Damage Response–Deficient Tumors

Ian M. Silverman, Joseph D. Schonhoft, Benjamin Herzberg, Arielle Yablonovitch, Errin Lagow et al. (22 authors)

2025-10-01

10.1158/1078-0432.c.8065145

Ataxia telangiectasia and Rad3-related (ATR) inhibitor camonsertib dose optimization in patients with biomarker-selected advanced solid tumors (TRESR study)

Elisa Fontana, Ezra Y. Rosen, Elizabeth K. Lee, Martin Højgaard, Niharika B. Mettu et al. (19 authors)

JNCI Journal of the National Cancer Institute2024-05-069 citations

10.1093/jnci/djae098

Discovery of the Potent and Selective ATR Inhibitor Camonsertib (RP-3500)

W. Cameron Black, Abbas Abdoli, Xiuli An, Anick Auger, Patrick Beaulieu et al. (37 authors)

Journal of Medicinal Chemistry2024-02-0121 citations

10.1021/acs.jmedchem.3c01917

Abstract B001: Identification of monoallelic <i>ATM</i> loss-of-function and homologous recombination deficiency (HRD) in high-grade ovarian tumor with prolonged response to camonsertib and low-dose gemcitabine combination therapy

Stéphanie Lheureux, Joseph D. Schonhoft, Ian M. Silverman, Julia Yang, Adrienne Johnson et al. (18 authors)

Cancer Research2024-01-091 citations

10.1158/1538-7445.dnarepair24-b001

Abstract B026: Detection and characterization of DDR reversion alterations in baseline tissue and plasma samples from patients enrolled in the TRESR and ATTACC Phase I clinical trials

Ian M. Silverman, Joseph D. Schonhoft, Esha Jain, Danielle Ulanet, Julia Yang et al. (17 authors)

Cancer Research2024-01-09

10.1158/1538-7445.dnarepair24-b026

Abstract B025: Exceptional response to the ataxia telangiectasia and Rad3-related inhibitor (ATRi), camonsertib, in a patient with alternative lengthening of telomeres (ALT)-positive metastatic melanoma

Timothy A. Yap, Ian M. Silverman, Adrienne Johnson, Chenfeng Meng, Joseph D. Schonhoft et al. (9 authors)

Cancer Research2024-01-09

10.1158/1538-7445.dnarepair24-b025

Development of a Practical Nomogram for Personalized Anemia Management in Patients Treated with Ataxia Telangiectasia and Rad3-related Inhibitor Camonsertib

Ezra Y. Rosen, Timothy A. Yap, Elizabeth K. Lee, Martin Højgaard, Niharika B. Mettu et al. (14 authors)

Clinical Cancer Research2023-12-115 citations

10.1158/1078-0432.ccr-23-2080

Abstract A123: Circulating tumor DNA (ctDNA) genomic and epigenomic profiling (GuardantINFINITY) for diagnosis of DNA damage repair (DDR) loss of function (LOF) and response monitoring in the TRESR and ATTACC trials

Ezra Y. Rosen, Joseph D. Schonhoft, Ian M. Silverman, Arielle Yablonovitch, Sunantha Sethuraman et al. (22 authors)

Molecular Cancer Therapeutics2023-12-011 citations

10.1158/1535-7163.targ-23-a123

Abstract B045: Ataxia telangiectasia- and Rad3-related kinase inhibitor (ATRi) camonsertib in combination with low dose gemcitabine in patients with solid tumors with DNA damage response (DDR) aberrations: Preclinical and Phase 1b results

Ezra Y. Rosen, Timothy A. Yap, Elisa Fontana, Elizabeth K. Lee, Devalingam Mahalingam et al. (23 authors)

Molecular Cancer Therapeutics2023-12-01

10.1158/1535-7163.targ-23-b045

Camonsertib in DNA damage response-deficient advanced solid tumors: phase 1 trial results.

Yap TA, Fontana E, Lee EK, Spigel DR, Højgaard M, Lheureux S, Mettu NB, Carneiro BA, Carter L, Plummer R, Cote GM, Meric-Bernstam F, O'Connell J, Schonhoft JD, Wainszelbaum M, Fretland AJ, Manley P, Xu Y, Ulanet D, Rimkunas V, Zinda M, Koehler M, Silverman IM, Reis-Filho JS, Rosen E.

2023-06-0567 citations

10.1038/s41591-023-02399-0

Abstract CT018: Safety and efficacy of three PARP inhibitors (PARPi) combined with the ataxia telangiectasia- and Rad3-related kinase inhibitor (ATRi) camonsertib in patients (pts) with solid tumors harboring DNA damage response (DDR) alterations

Timothy A. Yap, Siddhartha Yadav, Benjamin Herzberg, Benedito A. Carneiro, Elisa Fontana et al. (26 authors)

Cancer Research2023-04-147 citations

10.1158/1538-7445.am2023-ct018

ProTarget: a Danish Nationwide Clinical Trial on Targeted Cancer Treatment based on genomic profiling – a national, phase 2, prospective, multi-drug, non-randomized, open-label basket trial

T.M. Kringelbach, Martin Højgaard, Kristoffer Staal Rohrberg, Iben Spanggaard, Britt Elmedal Laursen et al. (20 authors)

BMC Cancer2023-02-2223 citations

10.1186/s12885-023-10632-9

ATR Inhibitor Camonsertib (RP-3500) Suppresses Early Stage Erythroblasts By Mediating Ferroptosis

Maayan Levy, Gino B. Ferraro, Li Li, Yongshuai Han, Lilian Varricchio et al. (11 authors)

Blood2022-11-157 citations

10.1182/blood-2022-169951

Abstract CT030: Genomic and pathologic determinants of response to RP-3500, an ataxia telangiectasia and Rad3-related inhibitor (ATRi), in patients (pts) with DNA damage repair (DDR) loss-of-function (LOF) mutant tumors in the Phase 1/2 TRESR trial

Timothy A. Yap, Ian M. Silverman, Elisa Fontana, Elizabeth Lee, David R. Spigel et al. (20 authors)

Cancer Research2022-06-1512 citations

10.1158/1538-7445.am2022-ct030

Circulating tumor DNA (ctDNA) determinants of improved outcomes in patients (pts) with advanced solid tumors receiving the ataxia telangiectasia and Rad3-related inhibitor (ATRi), RP-3500, in the phase 1/2a TRESR trial (NCT04497116).

Ezra Y. Rosen, Ian M. Silverman, Elisa Fontana, Elizabeth Katherine Lee, David R. Spigel et al. (19 authors)

Journal of Clinical Oncology2022-06-014 citations

10.1200/jco.2022.40.16_suppl.3082

RP-3500: A Novel, Potent, and Selective ATR Inhibitor that is Effective in Preclinical Models as a Monotherapy and in Combination with PARP Inhibitors.

Roulston A, Zimmermann M, Papp R, Skeldon A, Pellerin C, Dumas-Bérube É, Dumais V, Dorich S, Fader LD, Fournier S, Li L, Leclaire ME, Yin SY, Chefson A, Alam H, Yang W, Fugère-Desjardins C, Vignini-Hammond S, Skorey K, Mulani A, Rimkunas V, Veloso A, Hamel M, Stocco R, Mamane Y, Li Z, Young JTF, Zinda M, Black WC.

2021-12-1569 citations

10.1158/1535-7163.mct-21-0615

Abstract CC04-01: First-in-human biomarker-driven phase I TRESR trial of ataxia telangiectasia and Rad3-related inhibitor (ATRi) RP-3500 in patients (pts) with advanced solid tumors harboring synthetic lethal (SL) genomic alterations

Timothy A. Yap, Elizabeth Lee, David R. Spigel, Elisa Fontana, Martin Højgaard et al. (13 authors)

Molecular Cancer Therapeutics2021-12-014 citations

10.1158/1535-7163.targ-21-cc04-01

Abstract P054: RP-3500: A novel, potent and selective ATR inhibitor that is effective in pre-clinical models as a monotherapy and in combination with PARP inhibitors

Anne Roulston, Michal Zimmerman, Robert Papp, Alex Skeldon, Charles Pellerin et al. (28 authors)

Molecular Cancer Therapeutics2021-12-01

10.1158/1535-7163.targ-21-p054

Interventions

DRUGRP-3500 (camonsertib)

Oral ATR inhibitor

DRUGTalazoparib

Oral PARP inhibitor

DRUGGemcitabine Injection

Gemcitabine

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

Dose Escalation, expansion and phase 2

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* Written informed consent, according to local guidelines, signed and dated by the patient or legal guardian prior to the performance of any study-specific procedures, sampling, or analyses. * Male or female and ≥ 18 years-of-age at the time of signature of the consent. * Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1. * Histologically confirmed solid tumors resistant or refractory to standard treatment and/or patients who are intolerant to standard therapy. * Measurable disease as per RECIST v1.1 * Existing biomarker profile (tumor tissue or plasma) reported from a local test obtained in a certified lab per institutional guidelines: * Available tumor tissue * Ability to comply with the protocol and study procedures detailed in the Schedule of Assessments. * Ability to swallow and retain oral medications. * Acceptable organ function at screening * Acceptable blood counts at screening * Negative pregnancy test (serum) for females of childbearing potential at Screening and prior to first study drug. * Resolution of all toxicities of prior treatment or surgery. * Male patients with female partners of childbearing potential and females of childbearing potential must follow a contraception method (oral contraceptives allowed) during their participation in the study and for at least 6 months following last dose of study drug. Male patients must also refrain from donating sperm during their participation in the study and for 6 months following last dose of study drug. * Life expectancy ≥12 weeks after the start of the treatment according to the investigator's judgment. * Module 1c only: Ability to consume a high-fat meal and fast for 12 hours.

Exclusion criteria

* Chemotherapy, small molecule anticancer or biologic anticancer therapy given within 14 days prior to first dose of study drug. * History or current condition (such as transfusion dependent anemia or thrombocytopenia), therapy, or laboratory abnormality that might confound the study results, or interfere with the patient's participation for the full duration of the study treatment. * Prior therapy with an ATR or DNA-dependent protein kinase (DNA-PK) inhibitor. * Known hypersensitivity to any of the ingredients of RP-3500 (camonsertib). * Life-threatening illness, medical condition, active uncontrolled infection, or organ system dysfunction or other reasons which, in the investigator's opinion, could compromise the patient's safety. * Uncontrolled, symptomatic brain metastases. * Uncontrolled high blood pressure * Patients with active, uncontrolled bacterial, fungal, or viral infection, including hepatitis B virus (HBV), hepatitis C virus (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness. * Moderate or severe hepatic impairment (ie, Child-Pugh class B or C). * History or presence of an abnormal ECG that is clinically significant in the investigator's opinion. * History of ventricular dysrhythmias or risk factors such as structural heart disease, coronary heart disease (clinically significant electrolyte abnormalities or family history of sudden unexplained death or long QT syndrome * Current treatment with medications that are well-known to prolong the QT interval * History of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) diagnosis * Module 3 only: Known sensitivity to any of the ingredients of talazoparib.

Design outcomes

Primary

Measure	Time frame	Description
Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above	Start of treatment to 30 days post last dose, up to 1 year	Treatment-emergent adverse events (TEAEs) are those events that occur or worsen on or after the first dose of study drug up through 30 days post the last dose (or cross over to a different module) or the start of subsequent anticancer therapy. AEs are considered related to treatment if the relationship to camonsertib or the other combination drug (in the study regimen) is Related (include unknown relationship) as indicated on the AE eCRF page based on investigator's assessment.
Frequency of Dose Limiting Toxicity (DLT)	Either 21 days or 28 days (1 cycle) from the initiation of the study treatment.	Toxicity were assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. A toxicity was considered dose-limiting if it occurred during the first cycle and was deemed at least possibly related to study treatment. If multiple toxicities occurred, the most severe toxicity was used in the assessment. The DLT Evaluable population consists of patients who received at least 80% of planned total doses of camonsertib , 80% of planned total doses of camonsertib and talazoparib, or 80% of planned total doses of camonsertib and 100% of gemcitabine; complete all required safety evaluations and are observed through the end of Cycle 1; or patients who experience a DLT qualifying event in the first cycle of treatment.

Countries

Canada, Denmark, United Kingdom, United States

Participant flow

Participants by arm

Arm	Count
Module 1 Dose Schedule 1 Camonsertib 5 days on 2 days off Schedule \<=80 mg/day	7
Module 1 Dose Schedule 2 Camonsertib Monotherapy 5 days on 2 days off Schedule, 100 mg QD	8
Module 1 Dose Schedule 3 Camonsertib Monotherapy 5 days on 2 days off Schedule, 120 mg QD	6
Module 1 Dose Schedule 4 Camonsertib Monotherapy 5 days on 2 days off Schedule, 160 mg QD	3
Module 1 Dose Schedule 5 Camonsertib Monotherapy 5 days on 2 days off Schedule, 80 mg BID	1
Module 1 Dose Schedule 6 Camonsertib Monotherapy 3 days on 4 days off Schedule, 40 mg BID	1
Module 1 Dose Schedule 7 Camonsertib Monotherapy 3 days on 4 days off Schedule, 60 mg BID	4
Module 1 Dose Schedule 8 Camonsertib Monotherapy 3 days on 4 days off Schedule, 120 mg QD	25
Module 1 Dose Schedule 9 Camonsertib Monotherapy 3 days on 4 days off Schedule, 160 mg QD	67
Module 1 Dose Schedule 10 Camonsertib Monotherapy 3 days on 4 days off Schedule, 160 mg QD, 2 weeks on 1 week off	30
Module 1 Dose Schedule 11 Camonsertib Monotherapy 3 days on 4 days off Schedule, 200 mg QD, 2 weeks on 1 week off	5
Module 3a Dose Schedule 1 Talazoparib daily, Camonsertib Day 5 -7 , 3 weeks on schedule, Talazoparib 0.5 mg QD + Camonsertib 25 mg QD	2
Module 3a Dose Schedule 2 Talazoparib daily, Camonsertib Day 5 - 7, 3 weeks on, Talazoparib 0.25 mg QD + Camonsertib 25 mg BID	3
Module 3a Dose Schedule 3 Talazoparib daily, Camonsertib Day 5 - 7, 1 week on 1 week off Schedule, Talazoparib 0.25 mg QD + Camonsertib 50 mg QD	6
Module 3a Dose Schedule 4 Talazoparib daily, Camonsertib Day 5 - 7, 1 week on 1 week off Schedule, Talazoparib 0.25 mg QD + Camonsertib 80 mg QD	32
Module 4 Dose Schedule 1 Gemcitabine 400 mg/m2 + Camonsertib 80 mg QD 3 days on 4 days off, 2 weeks on 1 week off	5
Module 4 Dose Schedule 2 Gemcitabine 600 mg/m2 + Camonsertib 80 mg QD, 3 days on 4 days off, 2 weeks on 1 week off	6
Module 4 Dose Schedule 3 Gemcitabine 800 mg/m2 + Camonsertib 80 mg QD, 3 days on 4 days off, 2 weeks on 1 week off	2
Module 4 Dose Schedule 4 Gemcitabine 1000 mg/m2 + Camonsertib 80 mg QD, 3 days on 4 days off, 2 weeks on 1 week off	5
Module 4 Dose Schedule 5 Gemcitabine 400 mg/m2 + Camonsertib 80 mg QD, 3 days on 4 days off, 1 week on 1 week off	28
Module 4 Dose Schedule 6 Gemcitabine 400 mg/m2 + Camonsertib 80 mg QD, 2 days on 5 days off, 1 week on 1 week off	3
Module 4 Dose Schedule 7 Gemcitabine 100 mg/m2 + Camonsertib 120 mg QD, 2 days on 5 days off, 2 weeks on 1 week off	2
Module 4 Dose Schedule 8 Gemcitabine 100 mg/m2 + Camonsertib 80 mg QD, 2 days on 5 days off, 2 weeks on 1 week off	6
Module 4 Dose Schedule 9 Gemcitabine 200 mg/m2 + Camonsertib 80 mg QD, 2 days on 5 days off, 2 weeks on 1 week off	12
Module 4 Dose Schedule 10 Gemcitabine 200 mg/m2 + Camonsertib 80 mg QD, 2 days on 5 days off, 1 week on 1 week off	7
Total	276

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007	FG008	FG009	FG010	FG011	FG012	FG013	FG014	FG015	FG016	FG017	FG018	FG019	FG020	FG021	FG022	FG023	FG024
Overall Study	Clinical Progression Related	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Overall Study	Death	4	5	2	2	1	1	3	10	37	17	2	1	1	3	18	3	2	1	4	17	1	0	3	5	4
Overall Study	Lost to Follow-up	1	0	0	0	0	0	0	3	3	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Overall Study	Physician Decision	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Overall Study	Sponsor decision to terminate study	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Overall Study	Withdrawal by Subject	1	0	1	0	0	0	0	7	14	3	3	0	1	0	7	1	3	1	1	5	2	2	2	4	3

Baseline characteristics

Characteristic	Module 4 Dose Schedule 6	Total	Module 4 Dose Schedule 10	Module 4 Dose Schedule 9	Module 4 Dose Schedule 5	Module 4 Dose Schedule 4	Module 4 Dose Schedule 3	Module 4 Dose Schedule 2	Module 4 Dose Schedule 1	Module 3a Dose Schedule 4	Module 3a Dose Schedule 3	Module 3a Dose Schedule 2	Module 3a Dose Schedule 1	Module 1 Dose Schedule 11	Module 1 Dose Schedule 10	Module 1 Dose Schedule 9	Module 1 Dose Schedule 8	Module 1 Dose Schedule 7	Module 1 Dose Schedule 6	Module 1 Dose Schedule 5	Module 1 Dose Schedule 4	Module 1 Dose Schedule 3	Module 1 Dose Schedule 2	Module 1 Dose Schedule 1	Module 4 Dose Schedule 8	Module 4 Dose Schedule 7
Age, Customized Age	55 years	62 years	55 years	62.5 years	62.5 years	68 years	64 years	60.5 years	59 years	57 years	63 years	57 years	45.5 years	63 years	68 years	61 years	64 years	64.5 years	34 years	61 years	65 years	59 years	68 years	57 years	57.5 years	69 years
Eligibility Genotype ATM	1 Participants	82 Participants	1 Participants	2 Participants	4 Participants	1 Participants	0 Participants	3 Participants	1 Participants	4 Participants	3 Participants	2 Participants	1 Participants	1 Participants	11 Participants	25 Participants	5 Participants	4 Participants	0 Participants	1 Participants	1 Participants	3 Participants	3 Participants	4 Participants	1 Participants	0 Participants
Eligibility Genotype BRCA1	1 Participants	69 Participants	2 Participants	5 Participants	14 Participants	0 Participants	1 Participants	2 Participants	2 Participants	5 Participants	0 Participants	1 Participants	1 Participants	1 Participants	9 Participants	15 Participants	4 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	1 Participants	2 Participants	1 Participants
Eligibility Genotype BRCA2	1 Participants	54 Participants	3 Participants	4 Participants	5 Participants	3 Participants	0 Participants	0 Participants	1 Participants	15 Participants	1 Participants	0 Participants	0 Participants	1 Participants	3 Participants	8 Participants	4 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	2 Participants	1 Participants
Eligibility Genotype CDK12	0 Participants	14 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	1 Participants	1 Participants	3 Participants	3 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Eligibility Genotype CHEK2	0 Participants	4 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Eligibility Genotype IDH1	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Eligibility Genotype MRE11A	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Eligibility Genotype NBN	0 Participants	6 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	3 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Eligibility Genotype PALB2	0 Participants	11 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	3 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants
Eligibility Genotype RAD50	0 Participants	2 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Eligibility Genotype RAD51B	0 Participants	5 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Eligibility Genotype RAD51C	0 Participants	5 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Eligibility Genotype RNAseH2	0 Participants	8 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	2 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Eligibility Genotype SETD2	0 Participants	14 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	6 Participants	3 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	17 Participants	2 Participants	1 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	3 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	3 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	1 Participants	16 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	4 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	47 Participants	2 Participants	0 Participants	6 Participants	0 Participants	0 Participants	0 Participants	1 Participants	6 Participants	2 Participants	0 Participants	0 Participants	0 Participants	10 Participants	9 Participants	6 Participants	1 Participants	0 Participants	0 Participants	1 Participants	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	2 Participants	194 Participants	3 Participants	10 Participants	20 Participants	5 Participants	2 Participants	4 Participants	3 Participants	21 Participants	4 Participants	3 Participants	0 Participants	5 Participants	17 Participants	51 Participants	16 Participants	3 Participants	1 Participants	1 Participants	2 Participants	3 Participants	5 Participants	5 Participants	6 Participants	2 Participants
Sex: Female, Male Female	2 Participants	176 Participants	7 Participants	9 Participants	27 Participants	2 Participants	1 Participants	3 Participants	4 Participants	17 Participants	3 Participants	3 Participants	1 Participants	2 Participants	17 Participants	42 Participants	15 Participants	3 Participants	1 Participants	0 Participants	1 Participants	1 Participants	5 Participants	4 Participants	4 Participants	2 Participants
Sex: Female, Male Male	1 Participants	100 Participants	0 Participants	3 Participants	1 Participants	3 Participants	1 Participants	3 Participants	1 Participants	15 Participants	3 Participants	0 Participants	1 Participants	3 Participants	13 Participants	25 Participants	10 Participants	1 Participants	0 Participants	1 Participants	2 Participants	5 Participants	3 Participants	3 Participants	2 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk	EG011 affected / at risk	EG012 affected / at risk	EG013 affected / at risk	EG014 affected / at risk	EG015 affected / at risk	EG016 affected / at risk	EG017 affected / at risk	EG018 affected / at risk	EG019 affected / at risk	EG020 affected / at risk	EG021 affected / at risk	EG022 affected / at risk	EG023 affected / at risk	EG024 affected / at risk
deaths Total, all-cause mortality	4 / 7	7 / 8	3 / 6	2 / 3	1 / 1	1 / 1	3 / 4	10 / 25	41 / 67	16 / 30	3 / 5	1 / 2	1 / 3	3 / 6	18 / 32	3 / 5	2 / 6	1 / 2	4 / 5	17 / 28	1 / 3	0 / 2	3 / 6	5 / 12	4 / 7
other Total, other adverse events	6 / 7	8 / 8	6 / 6	3 / 3	1 / 1	1 / 1	4 / 4	23 / 25	65 / 67	29 / 30	5 / 5	2 / 2	3 / 3	6 / 6	32 / 32	5 / 5	6 / 6	2 / 2	5 / 5	28 / 28	3 / 3	2 / 2	6 / 6	12 / 12	7 / 7
serious Total, serious adverse events	1 / 7	4 / 8	3 / 6	0 / 3	0 / 1	1 / 1	1 / 4	5 / 25	20 / 67	9 / 30	2 / 5	1 / 2	1 / 3	1 / 6	11 / 32	2 / 5	4 / 6	1 / 2	2 / 5	10 / 28	2 / 3	1 / 2	3 / 6	5 / 12	2 / 7

Outcome results

Primary

Frequency of Dose Limiting Toxicity (DLT)

Toxicity were assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. A toxicity was considered dose-limiting if it occurred during the first cycle and was deemed at least possibly related to study treatment. If multiple toxicities occurred, the most severe toxicity was used in the assessment. The DLT Evaluable population consists of patients who received at least 80% of planned total doses of camonsertib , 80% of planned total doses of camonsertib and talazoparib, or 80% of planned total doses of camonsertib and 100% of gemcitabine; complete all required safety evaluations and are observed through the end of Cycle 1; or patients who experience a DLT qualifying event in the first cycle of treatment.

Time frame: Either 21 days or 28 days (1 cycle) from the initiation of the study treatment.

Population: Rate of DLT among DLT-evaluable population. DLT-evaluable population consists of patients who:~* Experience a DLT event or~* Received at least 80% of planned total doses of RP-3500 during Cycle 1 (Module 1), both RP-3500 and talazoparib (Module 3), or 80% of RP-3500 and 100% of gemcitabine (Module 4), complete all required safety evaluations, and are observed through the end of Cycle 1

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Cam<=80 5/2	Frequency of Dose Limiting Toxicity (DLT)	0 Participants
Cam100 5/2	Frequency of Dose Limiting Toxicity (DLT)	2 Participants
Cam120 5/2	Frequency of Dose Limiting Toxicity (DLT)	0 Participants
Cam160 5/2	Frequency of Dose Limiting Toxicity (DLT)	0 Participants
Cam80BID 5/2	Frequency of Dose Limiting Toxicity (DLT)	0 Participants
Cam40BID 3/4	Frequency of Dose Limiting Toxicity (DLT)	0 Participants
Cam60BID 3/4	Frequency of Dose Limiting Toxicity (DLT)	1 Participants
Cam120 3/4	Frequency of Dose Limiting Toxicity (DLT)	2 Participants
Cam160 3/4	Frequency of Dose Limiting Toxicity (DLT)	3 Participants
Cam160 2/1w	Frequency of Dose Limiting Toxicity (DLT)	2 Participants
Cam200 2/1w	Frequency of Dose Limiting Toxicity (DLT)	1 Participants
Tala0.5+Cam25	Frequency of Dose Limiting Toxicity (DLT)	2 Participants
Tala0.25+Cam25	Frequency of Dose Limiting Toxicity (DLT)	1 Participants
Tala0.25+Cam50	Frequency of Dose Limiting Toxicity (DLT)	0 Participants
Tala0.25+Cam80	Frequency of Dose Limiting Toxicity (DLT)	6 Participants
Gem400+Cam80 2/1	Frequency of Dose Limiting Toxicity (DLT)	5 Participants
Gem600+Cam80	Frequency of Dose Limiting Toxicity (DLT)	1 Participants
Gem800+Cam80	Frequency of Dose Limiting Toxicity (DLT)	0 Participants
Gem1000+Cam80	Frequency of Dose Limiting Toxicity (DLT)	2 Participants
Gem400+Cam80 1/1w	Frequency of Dose Limiting Toxicity (DLT)	7 Participants
Gem400+Cam80 2/5	Frequency of Dose Limiting Toxicity (DLT)	2 Participants
Gem100+Cam120	Frequency of Dose Limiting Toxicity (DLT)	1 Participants
Gem100+Cam80mg	Frequency of Dose Limiting Toxicity (DLT)	2 Participants
Gem200+Cam80 2/1w	Frequency of Dose Limiting Toxicity (DLT)	3 Participants
Gem200+Cam80 1/1w	Frequency of Dose Limiting Toxicity (DLT)	0 Participants

Primary

Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above

Treatment-emergent adverse events (TEAEs) are those events that occur or worsen on or after the first dose of study drug up through 30 days post the last dose (or cross over to a different module) or the start of subsequent anticancer therapy. AEs are considered related to treatment if the relationship to camonsertib or the other combination drug (in the study regimen) is Related (include unknown relationship) as indicated on the AE eCRF page based on investigator's assessment.

Time frame: Start of treatment to 30 days post last dose, up to 1 year

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Cam<=80 5/2	Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above	2 Participants
Cam100 5/2	Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above	5 Participants
Cam120 5/2	Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above	6 Participants
Cam160 5/2	Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above	2 Participants
Cam80BID 5/2	Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above	1 Participants
Cam40BID 3/4	Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above	1 Participants
Cam60BID 3/4	Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above	3 Participants
Cam120 3/4	Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above	8 Participants
Cam160 3/4	Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above	32 Participants
Cam160 2/1w	Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above	8 Participants
Cam200 2/1w	Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above	3 Participants
Tala0.5+Cam25	Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above	2 Participants
Tala0.25+Cam25	Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above	3 Participants
Tala0.25+Cam50	Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above	3 Participants
Tala0.25+Cam80	Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above	19 Participants
Gem400+Cam80 2/1	Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above	5 Participants
Gem600+Cam80	Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above	5 Participants
Gem800+Cam80	Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above	1 Participants
Gem1000+Cam80	Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above	5 Participants
Gem400+Cam80 1/1w	Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above	19 Participants
Gem400+Cam80 2/5	Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above	1 Participants
Gem100+Cam120	Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above	1 Participants
Gem100+Cam80mg	Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above	6 Participants
Gem200+Cam80 2/1w	Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above	9 Participants
Gem200+Cam80 1/1w	Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above	4 Participants

Study of RP-3500, Camonsertib, in Advanced Solid Tumors

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Intervention model description

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Countries

Participant flow

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Frequency of Dose Limiting Toxicity (DLT)

Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above